Locomotor activity

Last updated

Locomotor activity is a measure of animal behavior which is employed in scientific research. [1] [2]

Contents

Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in which locomotor activity (locomotion) is increased. [3] It is induced by certain drugs like psychostimulants and NMDA receptor antagonists and is reversed by certain other drugs like antipsychotics and certain antidepressants. [3] [4] [5] [6] Stimulation of locomotor activity is thought to be mediated by increased signaling in the nucleus accumbens. [7] [8]

Hypolocomotion, also known as locomotor hypoactivity, hypoactivity, and decreased locomotor activity, is an effect of certain drugs in animals in which locomotor activity is decreased. [9] It is a characteristic effect of many sedative agents and general anesthetics. Antipsychotics, which are dopamine receptor antagonists, and many serotonergic agents, such as meta-chlorophenylpiperazine (mCPP), can also produce this effect, often as a side effect.[ citation needed ]

Although locomotor activity is mainly an animal behavior test, it has also been evaluated in humans. [1] People with attention deficit hyperactivity disorder (ADHD), in the manic phase of bipolar disorder, on acute amphetamine, and with schizophrenia show increased locomotor activity, while children with autism show decreased locomotor activity. [1] Conversely, reduced locomotor activity is observed in bipolar individuals on mood stabilizers [1] and may be a characteristic symptom of the inattentive type of ADHD [10] (ADHD-PI) and sluggish cognitive tempo.[ citation needed ]

Drugs affecting locomotor activity

Dopaminergic agents

Dopamine releasing agents

Hyperlocomotion is induced by dopamine releasing agents (DRAs) and psychostimulants like amphetamine and methamphetamine. [3] [4] [5] [11] [12] These drugs likewise induce stereotypies. [3] [5]

Dopamine reuptake inhibitors

The dopamine reuptake inhibitors (DRIs) amineptine, bupropion, and nomifensine increase spontaneous locomotor activity in animals. [6] [13] The DRI cocaine increases locomotor activity similarly to the preceding DRIs and to amphetamines. [11] The atypical DRI modafinil does not produce hyperlocomotion in animals. [11]

Dopamine receptor agonists

Direct dopamine receptor agonists like apomorphine show biphasic effects, decreasing locomotor activity at low doses and increasing locomotor activity at high doses. [7]

Dopamine receptor antagonists

Drug-induced hyperlocomotion can be reversed by various drugs, such as antipsychotics acting as dopamine D2 receptor antagonists. [3] [5] Reversal of drug-induced hyperlocomotion has been used as an animal test of drug antipsychotic-like activity. [3] [5] Reversal of amphetamine- and NMDA receptor antagonist-induced stereotypies is also employed as a test of drug antipsychotic-like activity. [3] [5]

Adrenergic agents

Norepinephrine releasing agents

Selective norepinephrine releasing agents (NRAs) include ephedrine, pseudoephedrine, phenylpropanolamine, levomethamphetamine, and D-phenylalaninol. [14] [15] [16] [17] However, these drugs also release dopamine to a much lesser extent (e.g., ~10-fold less potently). [14] [15] [16] [17]

Ephedrine consistently stimulates locomotor activity in rodents. [18] [19] [20] However, the hyperlocomotion induced by ephedrine may be mediated by dopamine release rather than by norepinephrine release. [19] [21] On the other hand, lesioning the brain noradrenergic system with the noradrenergic neurotoxin DSP-4 reduces dextroamphetamine-induced hyperlocomotion. [22] [23] In addition, the selective α1-adrenergic receptor antagonist prazosin antagonizes amphetamine-induced hyperlocomotion [22] [24] and knockout of the α1B-adrenergic receptor dramatically reduces dextroamphetamine-induced hyperlocomotion. [22] [25] In contrast to ephedrine and amphetamine, pseudoephedrine [26] [27] and phenylpropanolamine do not stimulate locomotor activity in rodents. [28] [29] [30] However, in another study, pseudoephedrine was able to increase locomotor activity. [20] A potential confounding factor with β-hydroxyamphetamines like phenylpropanolamine, ephedrine, and pseudoephedrine is that they have lower lipophilicity compared to their amphetamine counterparts, with consequent reduced capacity to cross the blood–brain barrier and produce central nervous system effects. [31] [32] [33] [34]

Whereas dextromethamphetamine is a well-balanced norepinephrine–dopamine releasing agent (NDRA), levomethamphetamine is a selective NRA. [35] [14] [17] [36] Levomethamphetamine has similar potency as an NRA compared to dextromethamphetamine. [37] [11] [38] [39] [14] Conversely, levomethamphetamine is about 15- to 20-fold less potent in inducing dopamine release than dextromethamphetamine. [14] [17] [36] [35] [38] In accordance with the preceding, levomethamphetamine was found to selectively induce brain norepinephrine release with minimal effect on brain dopamine release across an assessed dosage range in rodents. [40] The drug did not increase locomotor activity at the assessed doses, in which brain dopamine release was not affected. [40] In contrast to levomethamphetamine, dextromethamphetamine at the same doses increased brain levels of both norepinephrine and dopamine and induced dose-dependent hyperlocomotion. [40] Relatedly, levomethamphetamine shows similar sympathomimetic effects as dextromethamphetamine but is substantially less potent as a psychostimulant in animals. [41] [42] [43] [40] As in rodents, levomethamphetamine showed reduced reinforcing and stimulant-like effects compared to dextromethamphetamine in rhesus monkeys. [44] [45]

Animal studies of the reinforcing and cocaine-like effects of dopamine releasing agents (DRAs) with varying capacities to release norepinephrine and serotonin in rodents and monkeys have suggested that in contrast to the case of serotonin release, which inhibits the reinforcing and stimulant-like effects of these agents, norepinephrine release has minimal influence on their misuse liability and associated effects. [46] [17] [47]

Norepinephrine reuptake inhibitors

Norepinephrine reuptake inhibitors (NRIs), like atomoxetine, reboxetine, and desipramine, do not increase locomotor activity in rodents and instead show no effect on locomotor activity or decrease it. [48] [49] [50] [51] [52] In addition, NRIs decrease amphetamine-, cocaine-, methylphenidate-, and phencyclidine (PCP)-induced hyperlocomotion in rodents. [53] [54] Accordingly, atomoxetine has been reported to attenuate the stimulant and rewarding effects of dextroamphetamine in humans. [55] [56]

A variety of different NRIs were shown to decrease spontaneous locomotor activity in a novel environment when given acutely and to decrease locomotor activity in both novel and familiar environments when given chronically in rodents. [49] Similarly, norepinephrine transporter (NET) knockout mice had low basal locomotor activity. [49] However, combination of an NRI with dopamine reuptake inhibition resulted in increased locomotor activity. [49] It was concluded that norepinephrine reuptake inhibition by itself decreases locomotor activity unless it is combined with dopamine reuptake inhibition. [49]

Serotonergic agents

Serotonin releasing agents

Certain serotonin releasing agents (SRAs), like MDMA and MDAI, though notably not others, like chlorphentermine, fenfluramine, and MMAI, [57] [15] [58] induce locomotor hyperactivity in animals. [59] [60] [61] [62] This is dependent on serotonin release allowed for by the serotonin transporter (SERT) and serotonin 5-HT2B receptor. [63] [60] [61] [64] [65] SERT knockout, pretreatment with serotonin reuptake inhibitors (SRIs) (which block MDMA-induced SERT-mediated serotonin release), or serotonin 5-HT2B receptor knockout (which likewise blocks MDMA-induced serotonin release), all completely block MDMA-induced locomotor hyperactivity. [63] [60] [61] [64] [65] In addition, locomotor hyperactivity produced by MDMA is partially attenuated by serotonin 5-HT1B receptor antagonism (or knockout) [63] [66] [67] or by serotonin 5-HT2A receptor antagonism. [68] [69] [70] The locomotor hyperactivity produced by MDMA is fully attenuated by combined serotonin 5-HT1B and 5-HT2A receptor antagonism. [69] Conversely, the serotonin 5-HT1A receptor is not involved in MDMA-induced hyperlocomotion. [60] Serotonin 5-HT2C receptor activation appears to inhibit MDMA-induced hyperlocomotion, and antagonism of this receptor has been reported to markedly enhance the locomotor hyperactivity induced by MDMA. [70] [69] [71] [72] Activation of the serotonin 5-HT2C receptor is known to inhibit dopamine release in the mesolimbic pathway as well as to inhibit dopamine release in the nigrostriatal and mesocortical pathways. [73] [74] [70] [75]

Although the serotonin system has been implicated in the hyperlocomotion of SRAs, certain SRAs, such as MDMA, are actually serotonin–norepinephrine–dopamine releasing agents (SNDRAs), and catecholaminergic mechanisms are likely to additionally be involved. [76] [77] Relatedly, the α1-adrenergic receptor antagonist prazosin completely blocks MDMA-induced hyperlocomotion in animals. [78] [77] [79] In addition, the α1-adrenergic receptor antagonists prazosin and doxazosin reduce the psychostimulant and/or euphoric effects of MDMA in humans. [80] [81] [82] Similarly, the norepinephrine reuptake inhibitor (NRI) reboxetine, which prevents MDMA from inducing norepinephrine release, likewise reduces the stimulant effects and emotional excitation of MDMA in humans. [78] [83] Dopamine receptors also appear to be involved in MDMA-induced hyperlocomotion, although findings in this area, both in animals and humans, seem to be conflicting. [78] [84] [85]

In contrast to non-selective SRAs like MDMA, the highly selective SRA MMAI induces hypolocomotion in animals. [86] Similarly, the highly selective SRA chlorphentermine is said to weakly stimulate locomotor activity at low doses and to progressively suppress locomotor activity at higher doses. [87]

The reasons for the differences in locomotor activity with different SRAs are not fully clear. [70] In any case, they may be related to factors such as whether the agents are selective SRAs, whether they additionally act as agonists of serotonin 5-HT2 receptors, and whether they additionally induce the release of norepinephrine and/or dopamine. [70] [88] [89] [63] [58] [86]

Serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) have been reported to have no effect or to increase locomotor activity, at least under certain circumstances like novel environments. [89] [49] [50] [52] However, in other studies, SSRIs have been reported to produce hypolocomotion, an effect that could be reversed by the serotonin 5-HT2C receptor antagonist SB-242084. [90] [91] [92] In another study, the SSRIs fluoxetine and citalopram had no effect on locomotor activity alone or in combination with SB-242084. [89]

Fluoxetine has been found to not affect dextroamphetamine-induced hyperlocomotion. [53] Similarly, sertraline did not affect cocaine-induced hyperlocomotion. [93]

Serotonin precursors

The serotonin precursor 5-hydroxytryptophan (5-HTP) combined with benserazide can suppress the hyperlocomotion induced by dextroamphetamine in rodents. [94]

Serotonin receptor agonists

The non-selective serotonin receptor agonists and serotonergic psychedelics LSD and DOI decrease locomotor activity in animals. [12] However, whereas LSD suppresses locomotion at all doses tested, DOI as well as DOM show an inverted U-shaped dose–response curve, with stimulation of locomotor activity at low doses and suppression of locomotion at higher doses. [12] [95] [96] [97] [98] The hyperlocomotion of DOI at low doses is abolished in serotonin 5-HT2A receptor knockout mice, whereas the hypolocomotion with DOI at higher doses is blocked by the selective serotonin 5-HT2C receptor antagonist SER-082. [12] [95] [97] Similarly, the hyperlocomotion of low doses of DOM is reduced by the serotonin 5-HT2A receptor antagonist volinanserin (MDL-100907) and enhanced by the serotonin 5-HT2C receptor antagonist SB-242084 and its hypolocomotion at high doses is attenuated by SB-242084. [96] As such, it has been concluded that serotonin 5-HT2A receptor activation increases locomotor activity while serotonin 5-HT2C receptor agonism decreases locomotor activity. [95] [96] [98]

The locomotor effects of many other serotonergic psychedelics have also been studied and have often been similar to the preceding agents. [97] However, in other cases, they have been different. [97] The tryptamine psychedelics psilocin and 5-MeO-DMT produce profound hypolocomotion in mice and this is blocked by the serotonin 5-HT1A receptor antagonist WAY-100635 or by serotonin 5-HT1A receptor knockout but not by the serotonin 5-HT2C receptor antagonist SB-242084. [97] 5-MeO-DALT dose-dependently increased locomotor activity but produced a sharp decrease at the highest tested dose. [99] The relatively selective serotonin 5-HT2A receptor agonist 25I-NBOMe has been found to show similar locomotor effects to phenylalkylamine psychedelics, increasing locomotor activity at low doses at decreasing it at higher doses. [98] [99] The selective serotonin 5-HT2A receptor agonist 25CN-NBOH modestly increased locomotor activity or did not affect it. [100] [101] [102]

The non-selective serotonin 5-HT2C receptor agonists meta-chlorophenylpiperazine (mCPP) and Ro60-0175 as well as the selective serotonin 5-HT2C receptor agonists WAY-161503 and CP-809101 produce hypolocomotion in rodents. [89] [103] [97] In serotonin 5-HT2C receptor knockout mice, on the other hand, mCPP produced hyperlocomotion. [89] In contrast to most serotonin 5-HT2C receptor agonists, the selective serotonin 5-HT2C receptor agonist WAY-163909 had no effect on spontaneous locomotor activity. [103] The selective serotonin 5-HT2C receptor agonists WAY-163909 and CP-809101 have been found to suppress dextroamphetamine-induced hyperlocomotion. [103] [104] The non-selective serotonin 5-HT2C receptor agonist Ro60-0175 has been found to suppress the hyperlocomotion induced by cocaine, and this effect could be blocked by the selective serotonin 5-HT2C receptor antagonist SB-242084. [89] CP-809101 has been found to decrease locomotor activity and antagonized phencyclidine (PCP)-induced hyperlocomotion. [104]

Serotonin receptor antagonists

Serotonin 5-HT2A receptor antagonists like volinanserin (MDL-100907) and ketanserin counteract the hyperactivity induced by amphetamine, cocaine, and NMDA receptor antagonists like PCP in animals. [105] [12] [106] [107] [108] [109] [110] [111] Less-selective serotonin 5-HT2A receptor antagonists, like trazodone, have been found to decrease locomotor and behavioral activity and to inhibit amphetamine-, cocaine-, and PCP-induced hyperactivity in animals similarly. [108] [112] [113] [114] [115] [6] Blockade of the serotonin 5-HT2A receptor by atypical antipsychotics like clozapine and olanzapine contributes to the hypolocomotion they produce. [97] [116] In addition to serotonin 5-HT2A receptor antagonists, serotonin 5-HT2A receptor biased agonists that selectively activate the β-arrestin pathway but not the Gq pathway, like 25N-N1-Nap, have been found to antagonize PCP-induced locomotor hyperactivity in rodents. [105]

Serotonin 5-HT2B receptor antagonists by themselves do not appear to affect locomotor activity. [117] However, antagonists of the serotonin 5-HT2B receptor decrease the locomotor hyperactivity of amphetamine, cocaine, and phencyclidine (PCP). [118] [119] [120] [121]

The selective serotonin 5-HT2C receptor antagonist SB-242084 has been found to produce modest hyperlocomotion at high doses in rodents. [122] [123] [97] The drug has also been found to produce modest stimulant-like effects in squirrel monkeys. [122] SB-242084 has additionally been found to enhance the hyperlocomotion of dextroamphetamine in rodents. [103] Similarly, it has been found to dose-dependently enhance the hyperlocomotion induced by dexfenfluramine in rodents. [89] [124] It has also been found to enhance the hyperlocomotion induced by MDMA, fenfluramine, cocaine, and methylphenidate, to modestly enhance nicotine- and morphine-induced hyperactivity, and to not affect the hyperactivity induced by RU-24969 or citalopram. [125] The serotonin 5-HT2C receptor antagonist SB-221284 has been found to augment the nucleus accumbens dopamine elevations and hyperlocomotion induced by NMDA receptor antagonists like phencyclidine (PCP) and dizocilpine (MK-801) in rodents. [126]

Glutamatergic agents

NMDA receptor antagonists

Hyperlocomotion is induced by NMDA receptor antagonists and dissociative hallucinogens such as phencyclidine (PCP), ketamine, and dizocilpine (MK-801). [3] [4] [5] [11] [12] These drugs likewise induce stereotypies. [3] [5]

Cholinergic agents

Muscarinic acetylcholine receptor antagonists

Non-selective muscarinic acetylcholine receptor antagonists, or antimuscarinics, such as atropine, hyoscyamine, and scopolamine, produce robust hyperactivity in animals, but also produce deliriant effects such as amnesia and hallucinations in both animals and humans. [127] [128]

Cannabinoids

Tetrahydrocannabinol (THC) produces hypolocomotion in rodents. [129] Cannabidiol (CBD) does not appear to affect locomotor activity when administered by itself or when added to THC. [129] However, in some studies, CBD augmented THC-induced hypolocomotion. [129]

Opioids

Classical opioids or μ-opioid receptor agonists like morphine and fentanyl stimulate locomotor activity in rodents. [130] [131] [132] However, high doses of μ-opioid receptor agonists induce locomotor depression. [133] δ-Opioid receptor agonists like AZD-2327 likewise stimulate locomotor activity in rodents. [134] [135]

TAAR1 modulators

The trace amine-associated receptor 1 (TAAR1) regulates the monoaminergic system and is a biological target for trace amines like β-phenethylamine and tyramine, the thyronamine 3-iodothyronamine, and drugs like amphetamines. [136] [137]

TAAR1 knockout mice show unchanged basal locomotor activity. [138] However, they show enhanced hyperlocomotion with amphetamine, methamphetamine, and MDMA, as well as with β-phenethylamine. [139] [140] [141] TAAR1 overexpression likewise is associated with unchanged basal locomotor activity. [142] However, overexpression of the TAAR1 results in only weak locomotor stimulation by amphetamine. [139] [143] [144] [145] The TAAR1 full agonists RO5256390, ulotaront (SEP-363856), and LK00764 have been found to suppress locomotion in mice. [146] [147] [148] Conversely, the TAAR1 full agonist RO5166017 [149] [150] and the TAAR1 partial agonists RO5073012, [145] RO5203648, [151] and RO5263397 on their own did not affect basal locomotion in rodents. [152] [153] [154] Similarly, RO5263397 did not affect locomotor activity in monkeys. [155] The TAAR1 antagonist EPPTB does not affect basal locomotor activity in rodents. [150] [156]

The TAAR1 full agonists RO5166017, RO5256390, and ulotaront all suppress psychostimulant-induced hyperlocomotion in mice. [139] [157] [158] The TAAR1 partial agonists RO5073012, RO5203648, and RO5263397 suppress locomotor stimulation induced by cocaine. [139] [143] [157] [159] The TAAR1 partial agonist RO5203648 suppressed dextroamphetamine-induced hyperlocomotion at the highest assessed dose in rats but did not affect dextroamphetamine-induced hyperactivity in mice. [144] [158] [142] [151] It showed complex effects on methamphetamine-induced hyperlocomotion in rats, reducing early but potentiating late methamphetamine-induced hyperlocomotion with acute administration and suppressing methamphetamine-induced hyperlocomotion with chronic administration. [144] [160] The dual TAAR1 full agonist and serotonin 5-HT1 receptor modulator ulotaront did not affect dextroamphetamine-induced hyperlocomotion in rats. [161] The TAAR1 weak partial agonist RO5073012 did not affect amphetamine-induced hyperlocomotion in mice but substantially restored the locomotor stimulation of amphetamine in mice with TAAR1 overexpression. [144] [143] [145] In an unpublished study, EPPTB was reported to considerably reduce methamphetamine-induced hyperlocomotion in mice chronically exposed to methamphetamine, an effect that was absent in TAAR1 knockout mice. [162] [163] The TAAR1 full agonists RO5166017, RO5256390, ulotaront, and LK00764 and the TAAR1 partial agonists RO5203648 and RO5263397 suppress the hyperlocomotion induced by NMDA receptor antagonists like phencyclidine (PCP), L-687,414, and dizocilpine (MK-801) in rodents. [144] [149] [159] [164] [148]

Other agents

Many tricyclic antidepressants (TCAs) do not increase locomotion, and instead often actually show behavioral sedation. [6] [7] [165]

Non-drug stimuli affecting locomotor activity

Light exposure has been found to increase locomotor activity and exploratory behavior in rodents. [166]

Similar behavioral measures

Other similar behavioral measures include stereotypy, exploratory behavior, climbing behavior, and jumping behavior. [167] [4] [5] Amphetamines, which are dopamine releasing agents (DRAs) induce stereotypies in addition to hyperlocomotion. [4] [5] The dopamine receptor agonist apomorphine induces stereotypy and climbing behavior. [4] The dopamine precursor levodopa (L-DOPA) induces jumping behavior. [4] These effects can all be reversed by antipsychotics, which are dopamine receptor antagonists. [4]

See also

Related Research Articles

<span class="mw-page-title-main">MDMA</span> Psychoactive drug, often called ecstasy

3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, and molly, is an empathogen–entactogenic drug with stimulant and minor psychedelic properties. In studies, it has been used alongside psychotherapy in the treatment of post-traumatic stress disorder (PTSD) and social anxiety in autism spectrum disorder. The purported pharmacological effects that may be prosocial include altered sensations, increased energy, empathy, and pleasure. When taken by mouth, effects begin in 30 to 45 minutes and last three to six hours.

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon. The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others.

<span class="mw-page-title-main">Empathogen</span> Class of psychoactive drugs that produce empathic experiences

Empathogens or entactogens are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4-methylenedioxymethamphetamine (MDMA). This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulants. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, GHB, αMT, and αET, MDAI among others. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used. Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.

<span class="mw-page-title-main">3,4-Methylenedioxyamphetamine</span> Empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family

3,4-Methylenedioxyamphetamine (MDA), sometimes referred to as sass, is an empathogen-entactogen, stimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.

<span class="mw-page-title-main">Phentermine</span> Weight loss medication

Phentermine, sold under the brand name Adipex-P among others, is a medication used together with diet and exercise to treat obesity. It is available by itself or as the combination phentermine/topiramate. Phentermine is taken by mouth.

<span class="mw-page-title-main">Aminorex</span> Chemical compound

Aminorex, sold under the brand names Menocil and Apiquel among others, is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension (PPH). In the United States, aminorex is a Schedule I controlled substance.

<span class="mw-page-title-main">Norfenfluramine</span> Never-marketed drug of the amphetamine family

Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.

<span class="mw-page-title-main">TAAR1</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene.

<span class="mw-page-title-main">SB-242084</span> Chemical compound

SB-242084 is a selective antagonist of the serotonin 5-HT2C receptor which is used in scientific research.

<i>para</i>-Chloroamphetamine Chemical compound

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) and serotonergic neurotoxin of the amphetamine family. It is used in scientific research in the study of the serotonin system, as a serotonin releasing agent (SRA) at lower doses to produce serotonergic effects, and as a serotonergic neurotoxin at higher doses to produce long-lasting depletions of serotonin.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">3-Methoxyamphetamine</span> Stimulant drug of the amphetamine class

3-Methoxyamphetamine (3-MA), also known as meta-methoxyamphetamine (MMA), is a monoamine releasing agent (MRA) of the amphetamine family. It is a positional isomer of para-methoxyamphetamine.

<span class="mw-page-title-main">RO5166017</span> Chemical compound

RO5166017, or RO-5166017, is a drug developed by Hoffmann-La Roche which acts as a potent and selective agonist for the trace amine-associated receptor 1 (TAAR1), with no significant activity at other targets. It is a partial agonist or near-full agonist depending on the species.

<span class="mw-page-title-main">EPPTB</span> Chemical compound

EPPTB, also known as RO5212773 or RO-5212773, is a drug developed by Hoffmann-La Roche which acts as a potent and selective antagonist or inverse agonist of the trace amine-associated receptor 1 (TAAR1). The drug was the first selective antagonist developed for the TAAR1. It is a potent agonist of the mouse and rat TAAR1, but is dramatically less potent as an agonist of the human TAAR1. EPPTB has been used in scientific research to demonstrate an important role for TAAR1 in regulation of dopaminergic signaling in the limbic system.

<i>o</i>-Phenyl-3-iodotyramine Chemical compound

o-Phenyl-3-iodotyramine (o-PIT) is a drug which acts as a selective agonist for the trace amine-associated receptor 1 (TAAR1). It has reasonable selectivity for TAAR1 but relatively low potency, and is rapidly metabolised in vivo, making it less useful for research than newer ligands such as RO5166017. Its EC50Tooltip half-maximal effective concentration values have been reported to be 35 nM for the mouse TAAR1, 2.4 nM at the rat TAAR1, and 9.5 nM at the human TAAR1.

<span class="mw-page-title-main">Monoaminergic activity enhancer</span> Class of compounds in the nervous system

Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of drugs that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs are distinct from monoamine releasing agents (MRAs) like amphetamine and fenfluramine in that they do not induce the release of monoamines from synaptic vesicles but rather potentiate only nerve impulse propagation-mediated monoamine release. That is, MAEs increase the amounts of monoamine neurotransmitters released by neurons per electrical impulse.

<span class="mw-page-title-main">RO5263397</span> TAAR1 agonist

RO5263397, or RO-5263397, is a trace amine-associated receptor 1 (TAAR1) partial or full agonist which is used in scientific research. It is the most well-studied of all of the synthetic TAAR1 ligands. In addition to its use in research, RO5263397 is or was under development for potential clinical use as a medication.

<span class="mw-page-title-main">RO5203648</span> Pharmaceutical compound

RO5203648 is a trace amine-associated receptor 1 (TAAR1) partial agonist. It is a potent and highly selective partial agonist of both rodent and primate TAAR1. The drug suppresses the effects of psychostimulants like cocaine and methamphetamine. It also produces a variety of other behavioral effects, such as antidepressant-like, antipsychotic-like, and antiaddictive effects. Research with RO5203648 has led to interest in TAAR1 agonists for potential treatment of drug addiction. RO5203648 itself was not developed for potential medical use due to poor expected human pharmacokinetics.

<span class="mw-page-title-main">RO5073012</span> Pharmaceutical compound

RO5073012 is a selective low-efficacy partial agonist of the trace amine-associated receptor 1 (TAAR1) which has been used in scientific research. TAAR1 partial agonists like RO5073012 can have agonist- or antagonist-like effects at the TAAR1 depending on the context and level of TAAR1 signaling.

References

  1. 1 2 3 4 Young JW, Minassian A, Geyer MA (2016). "Locomotor Profiling from Rodents to the Clinic and Back Again". Curr Top Behav Neurosci. Current Topics in Behavioral Neurosciences. 28: 287–303. doi:10.1007/7854_2015_5015. ISBN   978-3-319-33911-5. PMID   27418071.
  2. ↑ Klein CJ, Budiman T, Homberg JR, Verma D, Keijer J, van Schothorst EM (2022). "Measuring Locomotor Activity and Behavioral Aspects of Rodents Living in the Home-Cage". Front Behav Neurosci. 16: 877323. doi: 10.3389/fnbeh.2022.877323 . PMC   9021872 . PMID   35464142.
  3. 1 2 3 4 5 6 7 8 9 Castagné, Vincent; Moser, Paul C.; Porsolt, Roger D. (2009). "Preclinical Behavioral Models for Predicting Antipsychotic Activity". Advances in Pharmacology. Vol. 57. Elsevier. pp. 381–418. doi:10.1016/s1054-3589(08)57010-4. ISBN   978-0-12-378642-5. ISSN   1054-3589. PMID   20230767.
  4. 1 2 3 4 5 6 7 8 Ayyar P, Ravinder JR (June 2023). "Animal models for the evaluation of antipsychotic agents". Fundam Clin Pharmacol. 37 (3): 447–460. doi:10.1111/fcp.12855. PMID   36410728.
  5. 1 2 3 4 5 6 7 8 9 10 Yee BK, Singer P (October 2013). "A conceptual and practical guide to the behavioural evaluation of animal models of the symptomatology and therapy of schizophrenia". Cell Tissue Res. 354 (1): 221–246. doi:10.1007/s00441-013-1611-0. PMC   3791321 . PMID   23579553.
  6. 1 2 3 4 Tucker JC, File SE (1986). "The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents". Neurosci Biobehav Rev. 10 (2): 115–121. doi:10.1016/0149-7634(86)90022-9. PMID   3737024.
  7. 1 2 3 D'Aquila PS, Collu M, Gessa GL, Serra G (September 2000). "The role of dopamine in the mechanism of action of antidepressant drugs". Eur J Pharmacol. 405 (1–3): 365–373. doi:10.1016/s0014-2999(00)00566-5. PMID   11033341.
  8. ↑ Ikemoto S, Panksepp J (December 1999). "The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking". Brain Res Brain Res Rev. 31 (1): 6–41. doi:10.1016/s0165-0173(99)00023-5. PMID   10611493.
  9. ↑ "APA Dictionary of Psychology". dictionary.apa.org. Retrieved 2023-09-26.
  10. ↑ Diagnostic and statistical manual of mental disorders : DSM-5. Arlington, VA: American Psychiatric Association. 2013. ISBN   978-0-89042-554-1.
  11. 1 2 3 4 5 Nishino S, Kotorii N (2016). "Modes of Action of Drugs Related to Narcolepsy: Pharmacology of Wake-Promoting Compounds and Anticataplectics". Narcolepsy: A Clinical Guide (2nd ed.). Cham: Springer International Publishing. pp. 307–329. doi:10.1007/978-3-319-23739-8_22. ISBN   978-3-319-23738-1.
  12. 1 2 3 4 5 6 Hanks JB, González-Maeso J (January 2013). "Animal models of serotonergic psychedelics". ACS Chem Neurosci. 4 (1): 33–42. doi:10.1021/cn300138m. PMC   3547517 . PMID   23336043.
  13. ↑ Rampello, Liborio; Nicoletti, Ferdinando; Nicoletti, Francesco (2000). "Dopamine and Depression". CNS Drugs. 13 (1). Springer Science and Business Media LLC: 35–45. doi:10.2165/00023210-200013010-00004. ISSN   1172-7047.
  14. 1 2 3 4 5 Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". European Journal of Pharmacology. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID   14612135.
  15. 1 2 3 Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
  16. 1 2 Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA (October 2003). "In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates". J Pharmacol Exp Ther. 307 (1): 138–145. doi:10.1124/jpet.103.053975. PMID   12954796.
  17. 1 2 3 4 5 Kohut SJ, Jacobs DS, Rothman RB, Partilla JS, Bergman J, Blough BE (December 2017). "Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys". Psychopharmacology (Berl). 234 (23–24): 3455–3465. doi:10.1007/s00213-017-4731-5. PMC   5747253 . PMID   28889212. In the present experiments, two monoamine releasers, l-MA and PAL-329, were shown to produce cocaine-like discriminative-stimulus effects in monkeys, suggesting that they meet the above criteria. One of these compounds, l-MA, also has been shown to serve as a positive reinforcer in rodents (Yokel and Pickens 1973) and monkeys (Winger et al 1994), further confirming the overlap with behavioral effects of cocaine. Both compounds also exhibit an approximately 15-fold greater potency in releasing NE than DA, which may be therapeutically advantageous. For example, the subjective effects of l-MA in human studies are similar in some respects to those of d-MA. However, the subjective effects of the two isomers also differ in potentially important ways. While both l-MA and d-MA produce subjective ratings of "drug liking" and "good effects" in experienced stimulant users, only l-MA produces concomitant ratings of bad or aversive drug effects (Mendelson et al 2006), a factor which may limit its abuse liability.
  18. ↑ Marvola M, Kivirinta R (November 1978). "Pharmacokinetics and locomotor activity increasing effect of ephedrine in mice". Acta Pharmacol Toxicol (Copenh). 43 (5): 381–386. doi:10.1111/j.1600-0773.1978.tb02282.x. PMID   726903.
  19. 1 2 Zarrindast MR (September 1981). "Dopamine-like properties of ephedrine in rat brain". Br J Pharmacol. 74 (1): 119–122. doi:10.1111/j.1476-5381.1981.tb09962.x. PMC   2071871 . PMID   7196787.
  20. 1 2 Walker RB, Fitz LD, Williams LM, Linton H, Smith CC (May 1993). "The effect of ephedrine isomers and their oxazolidines on locomotor activity in rats". Gen Pharmacol. 24 (3): 669–673. doi:10.1016/0306-3623(93)90229-q. PMID   8365649.
  21. ↑ Wellman PJ, Miller DK, Livermore CL, Green TA, McMahon LR, Nation JR (January 1998). "Effects of (-)-ephedrine on locomotion, feeding, and nucleus accumbens dopamine in rats". Psychopharmacology (Berl). 135 (2): 133–140. doi:10.1007/s002130050494. PMID   9497018.
  22. 1 2 3 Weinshenker D, Schroeder JP (July 2007). "There and back again: a tale of norepinephrine and drug addiction". Neuropsychopharmacology. 32 (7): 1433–1451. doi:10.1038/sj.npp.1301263. PMID   17164822.
  23. ↑ Ogren SO, Archer T, Johansson C (December 1983). "Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat". Neurosci Lett. 43 (2–3): 327–31. doi:10.1016/0304-3940(83)90209-4. PMID   6687006.
  24. ↑ Snoddy AM, Tessel RE (October 1985). "Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice". Eur J Pharmacol. 116 (3): 221–228. doi:10.1016/0014-2999(85)90156-6. PMID   3878298.
  25. ↑ Drouin C, Darracq L, Trovero F, Blanc G, Glowinski J, Cotecchia S, Tassin JP (April 2002). "Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates". J Neurosci. 22 (7): 2873–2884. doi:10.1523/JNEUROSCI.22-07-02873.2002. PMC   6758308 . PMID   11923452.
  26. ↑ Akiba K, Satoh S, Matsumura H, Suzuki T, Kohno H, Tadano T, Kisara K (May 1982). "[Effect of d-pseudoephedrine on the central nervous system in mice]". Nihon Yakurigaku Zasshi (in Japanese). 79 (5): 401–408. doi:10.1254/fpj.79.401. PMID   6813205.
  27. ↑ Sa-Ih N, Reakkamnuan C, Samerphob N, Cheaha D, Niyomdecha S, Kumarnsit E (2020). "Local field potential power spectra and locomotor activity following treatment with pseudoephedrine in mice". Acta Neurobiol Exp (Wars). 80 (1): 19–31. doi:10.21307/ane-2020-002. PMID   32214271.
  28. ↑ Eisenberg MS, Maher TJ, Silverman HI (August 1987). "A comparison of the effects of phenylpropanolamine, d-amphetamine and d-norpseudoephedrine on open-field locomotion and food intake in the rat". Appetite. 9 (1): 31–37. doi:10.1016/0195-6663(87)90051-1. PMID   3662492.
  29. ↑ Wellman PJ, Shelton K, Schenk S (September 1989). "Self-administration of phenylpropanolamine (PPA) by rats previously trained to self-administer amphetamine". Pharmacol Biochem Behav. 34 (1): 187–191. doi:10.1016/0091-3057(89)90371-7. PMID   2626448.
  30. ↑ Wellman PJ (1990). "The pharmacology of the anorexic effect of phenylpropanolamine". Drugs Exp Clin Res. 16 (9): 487–495. PMID   2100250.
  31. ↑ Chua SS, Benrimoj SI, Triggs EJ (1989). "Pharmacokinetics of non-prescription sympathomimetic agents". Biopharm Drug Dispos. 10 (1): 1–14. doi:10.1002/bdd.2510100102. PMID   2647163.
  32. ↑ Bouchard R, Weber AR, Geiger JD (July 2002). "Informed decision-making on sympathomimetic use in sport and health". Clin J Sport Med. 12 (4): 209–224. doi:10.1097/00042752-200207000-00003. PMID   12131054.
  33. ↑ Bharate SS, Mignani S, Vishwakarma RA (December 2018). "Why Are the Majority of Active Compounds in the CNS Domain Natural Products? A Critical Analysis". J Med Chem. 61 (23): 10345–10374. doi:10.1021/acs.jmedchem.7b01922. PMID   29989814.
  34. ↑ Schep LJ, Slaughter RJ, Beasley DM (August 2010). "The clinical toxicology of metamfetamine". Clin Toxicol (Phila). 48 (7): 675–694. doi:10.3109/15563650.2010.516752. PMID   20849327. Metamfetamine acts in a manner similar to amfetamine, but with the addition of the methyl group to the chemical structure. It is more lipophilic (Log p value 2.07, compared with 1.76 for amfetamine),4 thereby enabling rapid and extensive transport across the blood–brain barrier.19
  35. 1 2 Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID   11071707.
  36. 1 2 Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT (October 2006). "Human pharmacology of the methamphetamine stereoisomers". Clin Pharmacol Ther. 80 (4): 403–420. doi:10.1016/j.clpt.2006.06.013. PMID   17015058. The stereoisomers of methamphetamine produce markedly different dopamine, norepinephrine, and serotonin responses in various brain regions in rats.41,42 d-Methamphetamine (2 mg/kg) is more potent in releasing caudate dopamine than l-methamphetamine (12 and 18 mg/kg). By use of in vitro uptake and release assays, d-methamphetamine (50% effective concentration [EC50], 24.5 ± 2.1 nmol/L) was 17 times more potent in releasing dopamine than l-methamphetamine (EC50, 416 ± 20 nmol/L) and significantly more potent in blocking dopamine uptake (inhibition constant [Ki ], 114 ± 11 nm versus 4840 ± 178 nm).12,13
  37. ↑ Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective". J Psychopharmacol. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC   3666194 . PMID   23539642.
  38. 1 2 Xue Z, Siemian JN, Zhu Q, Blough BE, Li JX (August 2019). "Further pharmacological comparison of D-methamphetamine and L-methamphetamine in rats: abuse-related behavioral and physiological indices". Behav Pharmacol. 30 (5): 422–428. doi:10.1097/FBP.0000000000000453. PMC   6529304 . PMID   30480551. When considered with neurochemical data that l-MA is similarly potent in releasing norepinephrine (NE) but 15- to 20-fold less potent in releasing dopamine (DA), as compared to d-MA (Kuczenski et al., 1995; Melega et al., 1999), l-MA may appear to carry lower abuse liability than d-MA.
  39. ↑ Kuczenski R, Segal DS, Cho AK, Melega W (February 1995). "Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine". The Journal of Neuroscience. 15 (2): 1308–1317. doi: 10.1523/jneurosci.15-02-01308.1995 . PMC   6577819 . PMID   7869099. Consistent with our past results, in response to 2 mg/kg D-AMPH, mean caudate extracellular DA increased approximately 15-fold to a peak concentration of 688 ± 121 nM during the initial 20 min interval, then returned to baseline over the next 3 hr. Similarly, in response to 2 mg/kg D-METH, DA increased to a peak concentration of 648 ± 71 nM during the initial 20 min interval and then declined toward baseline. In contrast, in response to both 6 mg/kg L-AMPH and 12 mg/kg L-METH, peak DA concentrations (508 ± 51 and 287 ± 49 nM, respectively) were delayed to the second 20 min interval, before returning toward baseline. [...] Similar to our previous results, 2 mg/kg D-AMPH increased NE to a maximum of 29.3 ± 3.1 nM, about 20-fold over baseline, during the second 20 min interval. L-AMPH (6 mg/kg) produced a comparable effect, increasing NE concentrations to 32.0 ± 8.9 nM. In contrast, D-METH promoted an increase in NE to 12.0 ± 1.2 nM which was significantly lower than all other groups, whereas L-METH promoted an increase to 64.8 ± 4.9 nM, which was significantly higher than all other groups.
  40. 1 2 3 4 Pauly RC, Bhimani RV, Li JX, Blough BE, Landavazo A, Park J (March 2023). "Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain". ACS Chem Neurosci. doi:10.1021/acschemneuro.2c00689. PMID   36976755.
  41. ↑ Biel, J. H.; Bopp, B. A. (1978). "Amphetamines: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. p. 1–39. doi:10.1007/978-1-4757-0510-2_1. ISBN   978-1-4757-0512-6. The configuration of the α-methyl group is also an important determinant of the stimulant activity. The dextro isomers of both amphetamine and methamphetamine are considerably more potent as stimulants than the levo isomers. Depending on the parameter measured, the potency difference may range from two- to tenfold (Taylor and Snyder, 1970; Snyder et at., 1970b; Svensson, 1971; Roth et at., 1954; Van Rossum, 1970; Moore, 1963). The anorexic activity of the dextro isomers also exceeds that of the levo isomers (Lawlor et at., 1969). However, the two isomers are approximately equipotent in eliciting certain peripheral effects, such as the vasoconstriction, vasopressor, and other cardiovascular effects (Roth et at., 1954; Swanson et at., 1943).
  42. ↑ Nishimura T, Takahata K, Kosugi Y, Tanabe T, Muraoka S (May 2017). "Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles". J Neural Transm (Vienna). 124 (5): 519–523. doi:10.1007/s00702-017-1694-y. PMC   5399046 . PMID   28213761. There have been no studies directly comparing the pharmacodynamics and pharmacokinetics of the methamphetamine enantiomers in mice. It is often suggested that dmethamphetamine exerts more potent physiological and pharmacological effects than l-methamphetamine does, and that the stimulating effects exerted by l-methamphetamine on the central nervous system are 2–10 times less potent than those of d-methamphetamine (Mendelson et al. 2006). The results of the present study indicated that psychostimulant effects induced by l-methamphetamine are lower than those elicited by one-tenth the dose of d-methamphetamine. In addition, plasma pharmacokinetic parameters and striatal concentrations of methamphetamine following administration of l-methamphetamine at 10 mg/ kg (which did not induce psychomotor activity) were approximately 11 and 16 times as high, respectively, as those following administration of 1 mg/kg d-methamphetamine. Despite the fact that there are differentiable psycho-stimulating effects between two enantiomers, no significant difference in plasma pharmacokinetic parameters was detected at 1 mg/kg.
  43. ↑ Siemian JN, Xue Z, Blough BE, Li JX (July 2017). "Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats". Psychopharmacology (Berl). 234 (14): 2167–2176. doi:10.1007/s00213-017-4623-8. PMC   5482751 . PMID   28386698.
  44. ↑ Jacobs DS, Blough BE, Kohut SJ (August 2021). "Reinforcing and Stimulant-Like Effects of Methamphetamine Isomers in Rhesus Macaques". J Pharmacol Exp Ther. 378 (2): 124–132. doi:10.1124/jpet.121.000548. PMC   8407528 . PMID   33986037.
  45. ↑ Kohut SJ, Bergman J, Blough BE (March 2016). "Effects of L-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys". Psychopharmacology (Berl). 233 (6): 1067–1075. doi:10.1007/s00213-015-4186-5. PMC   4761269 . PMID   26713332.
  46. ↑ Banks ML, Bauer CT, Blough BE, Rothman RB, Partilla JS, Baumann MH, Negus SS (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Exp Clin Psychopharmacol. 22 (3): 274–284. doi:10.1037/a0036595. PMC   4067459 . PMID   24796848.
  47. ↑ de Moura, Fernando Barreto; Sherwood, Alexander; Prisinzano, Thomas Edward; Kohut, Stephen John; Bergman, Jack (2018). "Intravenous Self-Administration of Synthetic Cathinones in Rhesus Monkeys". The FASEB Journal. 32 (S1). doi: 10.1096/fasebj.2018.32.1_supplement.550.3 . ISSN   0892-6638.
  48. ↑ Upadhyaya HP, Desaiah D, Schuh KJ, Bymaster FP, Kallman MJ, Clarke DO, Durell TM, Trzepacz PT, Calligaro DO, Nisenbaum ES, Emmerson PJ, Schuh LM, Bickel WK, Allen AJ (March 2013). "A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder". Psychopharmacology (Berl). 226 (2): 189–200. doi:10.1007/s00213-013-2986-z. PMC   3579642 . PMID   23397050.
  49. 1 2 3 4 5 6 Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D (November 2006). "The effects of norepinephrine transporter inactivation on locomotor activity in mice". Biol Psychiatry. 60 (10): 1046–1052. doi:10.1016/j.biopsych.2006.03.057. PMID   16893531.
  50. 1 2 Prinssen EP, Ballard TM, Kolb Y, Nicolas LB (September 2006). "The effects of serotonin reuptake inhibitors on locomotor activity in gerbils". Pharmacol Biochem Behav. 85 (1): 44–49. doi:10.1016/j.pbb.2006.07.005. PMID   16920181.
  51. ↑ Rogóz Z, Wróbel A, Krasicka-Domka M, Maj J (1999). "Pharmacological profile of reboxetine, a representative of new class of antidepressant drugs, selective noradrenaline reuptake inhibitor (NARI), given acutely". Pol J Pharmacol. 51 (5): 399–404. PMID   10817540.
  52. 1 2 Brocco M, Dekeyne A, Veiga S, Girardon S, Millan MJ (April 2002). "Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents". Pharmacol Biochem Behav. 71 (4): 667–680. doi:10.1016/s0091-3057(01)00701-8. PMID   11888558.
  53. 1 2 Tyler TD, Tessel RE (1980). "Norepinephrine uptake inhibitors as biochemically and behaviorally selective antagonists of the locomotor stimulation induced by indirectly acting sympathomimetic aminetic amines in mice". Psychopharmacology (Berl). 69 (1): 27–34. doi:10.1007/BF00426517. PMID   6771822.
  54. ↑ Harkin A, Morris K, Kelly JP, O'Donnell JM, Leonard BE (March 2001). "Modulation of MK-801-induced behaviour by noradrenergic agents in mice". Psychopharmacology (Berl). 154 (2): 177–188. doi:10.1007/s002130000630. PMID   11314680.
  55. ↑ Somaini L, Donnini C, Raggi MA, Amore M, Ciccocioppo R, Saracino MA, Kalluppi M, Malagoli M, Gerra ML, Gerra G (May 2011). "Promising medications for cocaine dependence treatment". Recent Pat CNS Drug Discov. 6 (2): 146–160. doi:10.2174/157488911795933893. PMID   21599628.
  56. ↑ Sofuoglu M, Poling J, Hill K, Kosten T (2009). "Atomoxetine attenuates dextroamphetamine effects in humans". Am J Drug Alcohol Abuse. 35 (6): 412–6. doi:10.3109/00952990903383961. PMC   2796580 . PMID   20014909.
  57. ↑ Rothman RB, Blough BE, Baumann MH (December 2006). "Dual dopamine-5-HT releasers: potential treatment agents for cocaine addiction". Trends Pharmacol Sci. 27 (12): 612–618. doi:10.1016/j.tips.2006.10.006. PMID   17056126.
  58. 1 2 Callaway CW, Wing LL, Nichols DE, Geyer MA (1993). "Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release". Psychopharmacology (Berl). 111 (2): 169–178. doi:10.1007/BF02245519. PMID   7870948.
  59. ↑ Callaway, C. W.; Nichols, D. E.; Paulus, M. P.; Geyer, M. A. (1991). "Serotonin Release is Responsible for the Locomotor Hyperactivity in Rats Induced by Derivatives of Amphetamine Related to MDMA". Serotonin: Molecular Biology, Receptors and Functional Effects. Basel: Birkhäuser Basel. pp. 491–505. doi:10.1007/978-3-0348-7259-1_49. ISBN   978-3-0348-7261-4.
  60. 1 2 3 4 Stove CP, De Letter EA, Piette MH, Lambert WE (August 2010). "Mice in ecstasy: advanced animal models in the study of MDMA". Curr Pharm Biotechnol. 11 (5): 421–433. doi:10.2174/138920110791591508. PMID   20420576.
  61. 1 2 3 Aguilar MA, García-Pardo MP, Parrott AC (January 2020). "Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy')". Brain Res. 1727: 146556. doi:10.1016/j.brainres.2019.146556. PMID   31734398.
  62. ↑ Fantegrossi WE, Godlewski T, Karabenick RL, Stephens JM, Ullrich T, Rice KC, Woods JH (March 2003). "Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine ("ecstasy") and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice". Psychopharmacology (Berl). 166 (3): 202–211. doi:10.1007/s00213-002-1261-5. hdl: 2027.42/41985 . PMID   12563544.
  63. 1 2 3 4 Martinez-Price, Diana; Krebs-Thomson, Kirsten; Geyer, Mark (1 January 2002). "Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies". Addiction Research & Theory. 10 (1). Informa UK Limited: 43–67. doi:10.1080/16066350290001704. ISSN   1606-6359.
  64. 1 2 Fox MA, Andrews AM, Wendland JR, Lesch KP, Holmes A, Murphy DL (December 2007). "A pharmacological analysis of mice with a targeted disruption of the serotonin transporter". Psychopharmacology (Berl). 195 (2): 147–166. doi:10.1007/s00213-007-0910-0. PMID   17712549.
  65. 1 2 Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (March 2008). "Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro". J Neurosci. 28 (11): 2933–2940. doi:10.1523/JNEUROSCI.5723-07.2008. PMC   6670669 . PMID   18337424.
  66. ↑ Rempel NL, Callaway CW, Geyer MA (May 1993). "Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release". Neuropsychopharmacology. 8 (3): 201–211. doi:10.1038/npp.1993.22. PMID   8099482.
  67. ↑ Scearce-Levie K, Viswanathan SS, Hen R (January 1999). "Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor". Psychopharmacology (Berl). 141 (2): 154–161. doi:10.1007/s002130050819. PMID   9952039.
  68. ↑ Liechti ME, Vollenweider FX (December 2001). "Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies". Hum Psychopharmacol. 16 (8): 589–598. doi:10.1002/hup.348. PMID   12404538.
  69. 1 2 3 Bankson MG, Cunningham KA (January 2002). "Pharmacological studies of the acute effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-HT(1B/1D) and 5-HT(2) receptors". Neuropsychopharmacology. 26 (1): 40–52. doi:10.1016/S0893-133X(01)00345-1. PMID   11751031.
  70. 1 2 3 4 5 Baumann MH, Clark RD, Rothman RB (August 2008). "Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain". Pharmacol Biochem Behav. 90 (2): 208–217. doi:10.1016/j.pbb.2008.02.018. PMC   2491560 . PMID   18403002.
  71. ↑ Conductier G, Crosson C, Hen R, Bockaert J, Compan V (June 2005). "3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221". Neuropsychopharmacology. 30 (6): 1056–1063. doi:10.1038/sj.npp.1300662. PMID   15668722.
  72. ↑ Ball KT, Rebec GV (October 2005). "Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats". Psychopharmacology (Berl). 181 (4): 676–687. doi:10.1007/s00213-005-0038-z. PMID   16001122.
  73. ↑ Rothman RB, Blough BE, Baumann MH (2008). "Dopamine/Serotonin releasers as medications for stimulant addictions". Serotonin–Dopamine Interaction: Experimental Evidence and Therapeutic Relevance. Progress in Brain Research. Vol. 172. pp. 385–406. doi:10.1016/S0079-6123(08)00919-9. ISBN   978-0-444-53235-0. PMID   18772043.{{cite book}}: |journal= ignored (help)
  74. ↑ Rothman RB, Blough BE, Baumann MH (December 2008). "Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction". Exp Clin Psychopharmacol. 16 (6): 458–474. doi:10.1037/a0014103. PMC   2683464 . PMID   19086767.
  75. ↑ Canal CE, Murnane KS (January 2017). "The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens". J Psychopharmacol. 31 (1): 127–143. doi:10.1177/0269881116677104. PMC   5445387 . PMID   27903793.
  76. ↑ Baumann MH, Wang X, Rothman RB (January 2007). "3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings". Psychopharmacology (Berl). 189 (4): 407–424. doi:10.1007/s00213-006-0322-6. PMC   1705495 . PMID   16541247.
  77. 1 2 Pritchard LM, Hensleigh E (2012). "Psychopharmacology and Neurotoxicology of Methamphetamine and 3,4-Methylenedioxymethamphetamine". In Rincón A (ed.). Amphetamines: Neurobiological Mechanisms, Pharmacology and Effects. Hauppauge [NY]: Nova Biomedical Books. pp. 1–43. ISBN   9781614703051. OCLC   726822553. OL   16643844W.
  78. 1 2 3 Sáez-Briones P, Hernández A (September 2013). "MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology". Curr Neuropharmacol. 11 (5): 521–534. doi:10.2174/1570159X11311050007. PMC   3763760 . PMID   24403876.
  79. ↑ Selken J, Nichols DE (April 2007). "Alpha1-adrenergic receptors mediate the locomotor response to systemic administration of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) in rats". Pharmacol Biochem Behav. 86 (4): 622–630. doi:10.1016/j.pbb.2007.02.006. PMC   1976288 . PMID   17363047.
  80. ↑ Baggott M, Galloway GP, Jang M, Didier R, Mendelson JE (June 2008). Alpha-1 noradrenergic receptors contribute to psychostimulant-like effects of MDMA in humans (Poster 14) (PDF). CPDD 70th Annual Scientific Meeting, The Caribe Hilton, San Juan, Puerto Rico, June 14-19, 2008. Archived from the original (PDF) on 30 July 2016.
  81. ↑ Baggott M, Galloway GP, Jang M, Didier R, Pournajafi-Nazarloo H, Carter CS (June 2008). 3, 4-methylenedioxymethamphetamine (MDMA,'Ecstasy') and prazosin interactions in humans. 70th Annual Meeting of the College on Problems of Drug Dependence, San Juan, Puerto Rico.
  82. ↑ Hysek CM, Fink AE, Simmler LD, Donzelli M, Grouzmann E, Liechti ME (October 2013). "α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans". J Clin Psychopharmacol. 33 (5): 658–666. doi:10.1097/JCP.0b013e3182979d32. PMID   23857311.
  83. ↑ Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME (August 2011). "The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans". Clin Pharmacol Ther. 90 (2): 246–255. doi:10.1038/clpt.2011.78. PMID   21677639.
  84. ↑ Kaur, Harpreet; Karabulut, Sedat; Gauld, James W.; Fagot, Stephen A.; Holloway, Kalee N.; Shaw, Hannah E.; Fantegrossi, William E. (1 September 2023). "Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder". Psychedelic Medicine. 1 (3): 166–185. doi:10.1089/psymed.2023.0023. ISSN   2831-4425. The role of DA in the abuse-related effects of psychostimulants is well established in animal models. Still, deletions of DA D1, D2, and D3 receptor genes in mice had minimal impact on MDMA-induced locomotor activity,97 and DAT inhibition did not affect neurocognitive effects of MDMA in cynomolgus monkeys.98 In humans, D2 receptor antagonists reduced amphetamine-induced and MDMA-induced euphoria only at doses that produced dysphoria on their own.99 Therefore, it seems likely that systems unrelated to DA may be principally responsible for the acute effects of MDMA.40
  85. ↑ Risbrough VB, Masten VL, Caldwell S, Paulus MP, Low MJ, Geyer MA (November 2006). "Differential contributions of dopamine D1, D2, and D3 receptors to MDMA-induced effects on locomotor behavior patterns in mice". Neuropsychopharmacology. 31 (11): 2349–2358. doi:10.1038/sj.npp.1301161. PMID   16855533.
  86. 1 2 Marona-Lewicka D, Nichols DE (June 1994). "Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan". Eur J Pharmacol. 258 (1–2): 1–13. doi:10.1016/0014-2999(94)90051-5. PMID   7925587.
  87. ↑ Ogren SO, Ross SB (October 1977). "Substituted amphetamine derivatives. II. Behavioural effects in mice related to monoaminergic neurones". Acta Pharmacol Toxicol (Copenh). 41 (4): 353–368. doi:10.1111/j.1600-0773.1977.tb02674.x. PMID   303437.
  88. ↑ Bankson MG, Cunningham KA (June 2001). "3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions". J Pharmacol Exp Ther. 297 (3): 846–852. doi:10.1016/S0022-3565(24)29607-5. PMID   11356903.
  89. 1 2 3 4 5 6 7 Higgins GA, Fletcher PJ (July 2015). "Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders". ACS Chem Neurosci. 6 (7): 1071–1088. doi:10.1021/acschemneuro.5b00025. PMID   25870913.
  90. ↑ Bagdy G, Graf M, Anheuer ZE, Modos EA, Kantor S (December 2001). "Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635". Int J Neuropsychopharmacol. 4 (04): 399–408. doi:10.1017/S1461145701002632. PMID   11806866.
  91. ↑ Yamauchi M, Tatebayashi T, Nagase K, Kojima M, Imanishi T (August 2004). "Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats". Pharmacol Biochem Behav. 78 (4): 683–689. doi:10.1016/j.pbb.2004.05.003. PMID   15301922.
  92. ↑ Shishkina GT, Iudina AM, Dygalo NN (2006). "[Effects of fluoxetine on locomotor activity: possible involvement of dopamine]". Zh Vyssh Nerv Deiat Im I P Pavlova (in Russian). 56 (4): 523–528. PMID   17025197.
  93. ↑ Reith ME, Wiener HL, Fischette CT (1991). "Sertraline and cocaine-induced locomotion in mice. I. Acute studies". Psychopharmacology (Berl). 103 (3): 297–305. doi:10.1007/BF02244282. PMID   2057535.
  94. ↑ Baumann MH, Williams Z, Zolkowska D, Rothman RB (April 2011). "Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat". Drug Alcohol Depend. 114 (2–3): 147–152. doi:10.1016/j.drugalcdep.2010.09.015. PMC   3044786 . PMID   21071157.
  95. 1 2 3 Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, Powell SB (July 2009). "5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice". Neuropsychopharmacology. 34 (8): 1958–1967. doi:10.1038/npp.2009.29. PMC   2697271 . PMID   19322172.
  96. 1 2 3 Zhu H, Wang L, Wang X, Yao Y, Zhou P, Su R (November 2024). "5-hydroxytryptamine 2C/1A receptors modulate the biphasic dose response of the head twitch response and locomotor activity induced by DOM in mice". Psychopharmacology (Berl). 241 (11): 2315–2330. doi:10.1007/s00213-024-06635-4. PMID   38916640.
  97. 1 2 3 4 5 6 7 8 Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Curr Top Behav Neurosci. Current Topics in Behavioral Neurosciences. 36: 159–199. doi:10.1007/7854_2016_466. ISBN   978-3-662-55878-2. PMC   5787039 . PMID   28224459.
  98. 1 2 3 Halberstadt AL (2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Curr Top Behav Neurosci. Current Topics in Behavioral Neurosciences. 32: 283–311. doi:10.1007/7854_2016_64. ISBN   978-3-319-52442-9. PMID   28097528.
  99. 1 2 Gatch MB, Dolan SB, Forster MJ (August 2017). "Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents". Behav Pharmacol. 28 (5): 375–385. doi:10.1097/FBP.0000000000000309. PMC   5498282 . PMID   28537942.
  100. ↑ Odland AU, Jessen L, Kristensen JL, Fitzpatrick CM, Andreasen JT (February 2021). "The 5-hydroxytryptamine 2A receptor agonists DOI and 25CN-NBOH decrease marble burying and reverse 8-OH-DPAT-induced deficit in spontaneous alternation". Neuropharmacology. 183: 107838. doi:10.1016/j.neuropharm.2019.107838. PMID   31693871.
  101. ↑ Jensen AA, Halberstadt AL, Märcher-Rørsted E, Odland AU, Chatha M, Speth N, Liebscher G, Hansen M, Bräuner-Osborne H, Palner M, Andreasen JT, Kristensen JL (July 2020). "The selective 5-HT2A receptor agonist 25CN-NBOH: Structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH". Biochem Pharmacol. 177: 113979. doi:10.1016/j.bcp.2020.113979. PMID   32298690.
  102. ↑ Buchborn T, Lyons T, Knöpfel T (2018). "Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice". Front Pharmacol. 9: 17. doi: 10.3389/fphar.2018.00017 . PMC   5808243 . PMID   29467649.
  103. 1 2 3 4 Jensen NH, Cremers TI, Sotty F (September 2010). "Therapeutic potential of 5-HT2C receptor ligands". ScientificWorldJournal. 10: 1870–1885. doi: 10.1100/tsw.2010.180 . PMC   5763985 . PMID   20852829.
  104. 1 2 Monck NJ, Kennett GA (2008). "5-HT2C ligands: recent progress". Prog Med Chem. Progress in Medicinal Chemistry. 46: 281–390. doi:10.1016/S0079-6468(07)00006-9. ISBN   978-0-444-53018-9. PMID   18381128.
  105. 1 2 Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun. 14 (1): 8221. doi:10.1038/s41467-023-44016-1. PMC   10724237 . PMID   38102107.
  106. ↑ Carlsson ML (1995). "The selective 5-HT2A receptor antagonist MDL 100,907 counteracts the psychomotor stimulation ensuing manipulations with monoaminergic, glutamatergic or muscarinic neurotransmission in the mouse--implications for psychosis". J Neural Transm Gen Sect. 100 (3): 225–237. doi:10.1007/BF01276460. PMID   8748668.
  107. ↑ O'Neill MF, Heron-Maxwell CL, Shaw G (June 1999). "5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB". Pharmacol Biochem Behav. 63 (2): 237–243. doi:10.1016/s0091-3057(98)00240-8. PMID   10371652.
  108. 1 2 Gleason SD, Shannon HE (January 1997). "Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice". Psychopharmacology (Berl). 129 (1): 79–84. doi:10.1007/s002130050165. PMID   9122367.
  109. ↑ Ninan I, Kulkarni SK (October 1998). "5-HT2A receptor antagonists block MK-801-induced stereotypy and hyperlocomotion". Eur J Pharmacol. 358 (2): 111–116. doi:10.1016/s0014-2999(98)00591-3. PMID   9808259.
  110. ↑ McMahon LR, Cunningham KA (April 2001). "Antagonism of 5-hydroxytryptamine(2a) receptors attenuates the behavioral effects of cocaine in rats". J Pharmacol Exp Ther. 297 (1): 357–363. doi:10.1016/S0022-3565(24)29546-X. PMID   11259563.
  111. ↑ Herges S, Taylor DA (March 1998). "Involvement of serotonin in the modulation of cocaine-induced locomotor activity in the rat". Pharmacol Biochem Behav. 59 (3): 595–611. doi:10.1016/s0091-3057(97)00473-5. PMID   9512061.
  112. ↑ Ayd FJ, Settle EC (1982). "Trazodone: a novel, broad-spectrum antidepressant". Mod Probl Pharmacopsychiatry. Modern Trends in Pharmacopsychiatry. 18: 49–69. doi:10.1159/000406236. ISBN   978-3-8055-3428-4. PMID   6124884.
  113. ↑ Rawls WN (January 1982). "Trazodone (Desyrel, Mead-Johnson Pharmaceutical Division)". Drug Intell Clin Pharm. 16 (1): 7–13. doi:10.1177/106002808201600102. PMID   7032872.
  114. ↑ Al-Yassiri MM, Ankier SI, Bridges PK (June 1981). "Trazodone--a new antidepressant". Life Sci. 28 (22): 2449–2458. doi:10.1016/0024-3205(81)90586-5. PMID   7019617.
  115. ↑ Baran L, Maj J, Rogóz Z, Skuza G (1979). "On the central antiserotonin action of trazodone". Pol J Pharmacol Pharm. 31 (1): 25–33. PMID   482164.
  116. ↑ McOmish CE, Lira A, Hanks JB, Gingrich JA (December 2012). "Clozapine-induced locomotor suppression is mediated by 5-HT2A receptors in the forebrain". Neuropsychopharmacology. 37 (13): 2747–2755. doi:10.1038/npp.2012.139. PMC   3499715 . PMID   22871913.
  117. ↑ Gleason SD, Lucaites VL, Shannon HE, Nelson DL, Leander JD (December 2001). "m-CPP hypolocomotion is selectively antagonized by compounds with high affinity for 5-HT(2C) receptors but not 5-HT(2A) or 5-HT(2B) receptors". Behav Pharmacol. 12 (8): 613–620. doi:10.1097/00008877-200112000-00005. PMID   11856898.
  118. ↑ Cooper, Ignatius Alvarez; Beecher, Kate; Bartlett, Selena E.; Belmer, Arnauld (2021). "Role of the Serotonin 2B Receptor in the Reinforcing Effects of Psychostimulants". 5-HT2B Receptors. Vol. 35. Cham: Springer International Publishing. pp. 309–322. doi:10.1007/978-3-030-55920-5_18. ISBN   978-3-030-55919-9.
  119. ↑ Wang Q, Zhou Y, Huang J, Huang N (January 2021). "Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor". Pharmaceuticals (Basel). 14 (2): 76. doi: 10.3390/ph14020076 . PMC   7909583 . PMID   33498477.
  120. ↑ Auclair AL, Cathala A, Sarrazin F, Depoortère R, Piazza PV, Newman-Tancredi A, Spampinato U (September 2010). "The central serotonin 2B receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity". J Neurochem. 114 (5): 1323–1332. doi:10.1111/j.1471-4159.2010.06848.x. PMID   20534001.
  121. ↑ Devroye C, Cathala A, Di Marco B, Caraci F, Drago F, Piazza PV, Spampinato U (October 2015). "Central serotonin(2B) receptor blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical dopamine outflow". Neuropharmacology. 97: 329–337. doi:10.1016/j.neuropharm.2015.06.012. PMID   26116760.
  122. 1 2 Manvich DF, Kimmel HL, Cooper DA, Howell LL (September 2012). "The serotonin 2C receptor antagonist SB 242084 exhibits abuse-related effects typical of stimulants in squirrel monkeys". The Journal of Pharmacology and Experimental Therapeutics. 342 (3): 761–769. doi:10.1124/jpet.112.195156. PMC   3422522 . PMID   22685342. There is also evidence to support our finding that administration of SB 242084 alone induces stimulant-like effects, because administration of a high dose of SB 242084 (1.0 mg/kg) significantly increased basal locomotor activity in rats (Zaniewska et al., 2009). [...] This discrepancy may be accounted for by highlighting the tested dose range within each experiment. For example, the dose of SB 242084 used for reinstatement experiments in the previous rodent study (0.5 mg/kg) also failed to induce significant locomotor effects (Fletcher et al., 2002). However, increasing the dose of SB 242084 to 1.0 mg/kg did produce a modest, but significant, effect on locomotor activity in a separate study (Zaniewska et al., 2009).
  123. ↑ Zaniewska M, McCreary AC, Filip M (August 2009). "Interactions of serotonin (5-HT)2 receptor-targeting ligands and nicotine: locomotor activity studies in rats". Synapse. 63 (8): 653–661. doi:10.1002/syn.20645. PMID   19347958.
  124. ↑ Higgins GA, Ouagazzal AM, Grottick AJ (June 2001). "Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT(2) agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramine". Br J Pharmacol. 133 (4): 459–466. doi:10.1038/sj.bjp.0704082. PMC   1572804 . PMID   11399662.
  125. ↑ Fletcher PJ, Sinyard J, Higgins GA (September 2006). "The effects of the 5-HT(2C) receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists". Psychopharmacology (Berl). 187 (4): 515–525. doi:10.1007/s00213-006-0453-9. PMID   16832658.
  126. ↑ Hutson PH, Barton CL, Jay M, Blurton P, Burkamp F, Clarkson R, Bristow LJ (September 2000). "Activation of mesolimbic dopamine function by phencyclidine is enhanced by 5-HT(2C/2B) receptor antagonists: neurochemical and behavioural studies". Neuropharmacology. 39 (12): 2318–2328. doi:10.1016/s0028-3908(00)00089-7. PMID   10974315.
  127. ↑ Volgin AD, Yakovlev OA, Demin KA, Alekseeva PA, Kyzar EJ, Collins C, Nichols DE, Kalueff AV (January 2019). "Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models". ACS Chem Neurosci. 10 (1): 143–154. doi:10.1021/acschemneuro.8b00433. PMID   30252437.
  128. ↑ Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV (May 2019). "DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens". ACS Chem Neurosci. 10 (5): 2144–2159. doi:10.1021/acschemneuro.8b00615. PMID   30566832.
  129. 1 2 3 Calapai F, Cardia L, Calapai G, Di Mauro D, Trimarchi F, Ammendolia I, Mannucci C (April 2022). "Effects of Cannabidiol on Locomotor Activity". Life (Basel). 12 (5): 652. Bibcode:2022Life...12..652C. doi: 10.3390/life12050652 . PMC   9144881 . PMID   35629320.
  130. ↑ Steidl S, Wasserman DI, Blaha CD, Yeomans JS (December 2017). "Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons". Neurosci Biobehav Rev. 83: 72–82. doi:10.1016/j.neubiorev.2017.09.022. PMC   5730464 . PMID   28951251.
  131. ↑ Fujita M, Ide S, Ikeda K (September 2019). "Opioid and nondopamine reward circuitry and state-dependent mechanisms". Ann N Y Acad Sci. 1451 (1): 29–41. Bibcode:2019NYASA1451...29F. doi:10.1111/nyas.13605. PMID   29512887.
  132. ↑ Santos EJ, Banks ML, Negus SS (July 2022). "Role of Efficacy as a Determinant of Locomotor Activation by Mu Opioid Receptor Ligands in Female and Male Mice". J Pharmacol Exp Ther. 382 (1): 44–53. doi:10.1124/jpet.121.001045. PMC   9341253 . PMID   35489781.
  133. ↑ Shaykin JD, Denehy ED, Martin JR, Chandler CM, Luo D, Taylor CE, Sunshine MD, Turner JR, Alilain WJ, Prisinzano TE, Bardo MT (September 2024). "Targeting α1- and α2-adrenergic receptors as a countermeasure for fentanyl-induced locomotor and ventilatory depression". Environ Toxicol Pharmacol. 110: 104527. doi:10.1016/j.etap.2024.104527. PMC  11423298. PMID   39106924.
  134. ↑ Broom DC, Jutkiewicz EM, Rice KC, Traynor JR, Woods JH (September 2002). "Behavioral effects of delta-opioid receptor agonists: potential antidepressants?". Jpn J Pharmacol. 90 (1): 1–6. doi:10.1254/jjp.90.1. PMID   12396021.
  135. ↑ Dripps IJ, Jutkiewicz EM (2018). "Delta Opioid Receptors and Modulation of Mood and Emotion". Delta Opioid Receptor Pharmacology and Therapeutic Applications. Handbook of Experimental Pharmacology. Vol. 247. pp. 179–197. doi:10.1007/164_2017_42. ISBN   978-3-319-95131-7. PMID   28993835.
  136. ↑ Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacol Rev. 70 (3): 549–620. doi:10.1124/pr.117.015305. PMID   29941461.
  137. ↑ Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601.
  138. ↑ Lindemann L, Meyer CA, Jeanneau K, Bradaia A, Ozmen L, Bluethmann H, Bettler B, Wettstein JG, Borroni E, Moreau JL, Hoener MC (March 2008). "Trace amine-associated receptor 1 modulates dopaminergic activity". J Pharmacol Exp Ther. 324 (3): 948–956. doi:10.1124/jpet.107.132647. PMID   18083911.
  139. 1 2 3 4 Halff EF, Rutigliano G, Garcia-Hidalgo A, Howes OD (January 2023). "Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders". Trends Neurosci. 46 (1): 60–74. doi:10.1016/j.tins.2022.10.010. PMID   36369028. In addition to enhanced dopamine release, TAAR1-KO mice show enhanced hyperlocomotion in response to psychostimulant drugs including amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) [19,20,41,55], as well as to drugs that increase monoamine levels, such as MAO inhibitors [56]. By contrast, TAAR1-OE animals are hyposensitive to the stimulatory effects of amphetamine [54] in comparison to wild-type animals. [...] Three TAAR1 full agonists, RO5166017, RO5256390, and SEP-363856, were all able to prevent psychostimulant-induced hyperlocomotion in wild-type but not TAAR1-KO mice [47,78,79].
  140. ↑ Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T, Svenningsson P, Brocco M, Gobert A, De Groote L, Cistarelli L, Veiga S, De Montrion C, Rodriguez M, Galizzi JP, Lockhart BP, Cogé F, Boutin JA, Vayer P, Verdouw PM, Groenink L, Millan MJ (November 2011). "Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA)". J Neurosci. 31 (47): 16928–16940. doi:10.1523/JNEUROSCI.2502-11.2011. PMC   6623861 . PMID   22114263.
  141. ↑ Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP (October 2007). "The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia". Genes Brain Behav. 6 (7): 628–639. doi:10.1111/j.1601-183X.2006.00292.x. PMID   17212650. Most notably, Caron & Gainetdinov (personal communication) have recently observed that group-housed TA1 KO mice show enhanced sensitivity to the locomotor stimulating effects of both amphetamine and b-PEA relative to group-housed WT littermates, as well as normal habituation to an open field.
  142. 1 2 Pei Y, Asif-Malik A, Canales JJ (2016). "Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications". Front Neurosci. 10: 148. doi: 10.3389/fnins.2016.00148 . PMC   4820462 . PMID   27092049.
  143. 1 2 3 Jing L, Li JX (August 2015). "Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction". Eur J Pharmacol. 761: 345–352. doi:10.1016/j.ejphar.2015.06.019. PMC   4532615 . PMID   26092759.
  144. 1 2 3 4 5 Wu R, Li JX (December 2021). "Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders". CNS Drugs. 35 (12): 1239–1248. doi:10.1007/s40263-021-00871-4. PMC   8787759 . PMID   34766253.
  145. 1 2 3 Revel FG, Meyer CA, Bradaia A, Jeanneau K, Calcagno E, André CB, Haenggi M, Miss MT, Galley G, Norcross RD, Invernizzi RW, Wettstein JG, Moreau JL, Hoener MC (November 2012). "Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine". Neuropsychopharmacology. 37 (12): 2580–2592. doi:10.1038/npp.2012.109. PMC   3473323 . PMID   22763617.
  146. ↑ Shabani S, Houlton S, Ghimire B, Tonello D, Reed C, Baba H, Aldrich S, Phillips TJ (September 2023). "Robust aversive effects of trace amine-associated receptor 1 activation in mice". Neuropsychopharmacology. 48 (10): 1446–1454. doi:10.1038/s41386-023-01578-4. PMC   10425385 . PMID   37055488.
  147. ↑ Kuvarzin SR, Sukhanov I, Onokhin K, Zakharov K, Gainetdinov RR (July 2023). "Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders". Biomedicines. 11 (7): 1977. doi: 10.3390/biomedicines11071977 . PMC   10377193 . PMID   37509616.
  148. 1 2 Krasavin M, Lukin A, Sukhanov I, Gerasimov AS, Kuvarzin S, Efimova EV, Dorofeikova M, Nichugovskaya A, Matveev A, Onokhin K, Zakharov K, Gureev M, Gainetdinov RR (November 2022). "Discovery of Trace Amine Associated Receptor 1 (TAAR1) Agonist 2-(5-(4'-Chloro-[1,1'-biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)ethan-1-amine (LK00764) for the Treatment of Psychotic Disorders". Biomolecules. 12 (11). doi: 10.3390/biom12111650 . PMC   9687812 . PMID   36359001.
  149. 1 2 Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC (May 2011). "TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity". Proc Natl Acad Sci U S A. 108 (20): 8485–8490. Bibcode:2011PNAS..108.8485R. doi: 10.1073/pnas.1103029108 . PMC   3101002 . PMID   21525407.
  150. 1 2 Liu J, Wu R, Seaman R, Manz KM, Johnson B, Vu J, Huang Y, Zhang Y, Robison AJ, Neve R, Grueter BA, Dietz D, Li JX (April 2022). "TAAR1 regulates drug-induced reinstatement of cocaine-seeking via negatively modulating CaMKIIα activity in the NAc". Mol Psychiatry. 27 (4): 2136–2145. doi:10.1038/s41380-022-01448-3. PMC   9829124 . PMID   35079125.
  151. 1 2 Revel FG, Moreau JL, Gainetdinov RR, Ferragud A, Velázquez-Sánchez C, Sotnikova TD, Morairty SR, Harmeier A, Groebke Zbinden K, Norcross RD, Bradaia A, Kilduff TS, Biemans B, Pouzet B, Caron MG, Canales JJ, Wallace TL, Wettstein JG, Hoener MC (December 2012). "Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics". Biol Psychiatry. 72 (11): 934–942. doi:10.1016/j.biopsych.2012.05.014. PMID   22705041. Psychostimulants like cocaine and d-amphetamine interact with the DA transporter (DAT) to elevate extracellular DA concentration. In rodents, this translates into excessive [locomotor activity (LMA)] (Figures 2A, B; Figure S3A, B in Supplement 1), the reversal of which can be used to predict the potential antipsychotic activity of drugs (22). RO5203648 given orally reduced hyperlocomotion in both rats and mice treated with cocaine (Figure 2A, B), although not at the highest dose in mice (10 mg/kg). RO5203648 reduced d-amphetamine-induced hyperlocomotion by one half at a high dose (30 mg/kg) in rats, whereas in mice it had no effect at the doses tested (Figure S3A, B in Supplement 1).
  152. ↑ Thorn DA, Jing L, Qiu Y, Gancarz-Kausch AM, Galuska CM, Dietz DM, Zhang Y, Li JX (September 2014). "Effects of the trace amine-associated receptor 1 agonist RO5263397 on abuse-related effects of cocaine in rats". Neuropsychopharmacology. 39 (10): 2309–2316. doi:10.1038/npp.2014.91. PMC   4138753 . PMID   24743376.
  153. ↑ Jing L, Zhang Y, Li JX (October 2014). "Effects of the trace amine associated receptor 1 agonist RO5263397 on abuse-related behavioral indices of methamphetamine in rats". Int J Neuropsychopharmacol. 18 (4): pyu060. doi:10.1093/ijnp/pyu060. PMC   4360231 . PMID   25522401.
  154. ↑ Black SW, Schwartz MD, Chen TM, Hoener MC, Kilduff TS (November 2017). "Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics". Biol Psychiatry. 82 (9): 623–633. doi:10.1016/j.biopsych.2016.10.012. PMC   5395352 . PMID   27919403.
  155. ↑ Goonawardena AV, Morairty SR, Dell R, Orellana GA, Hoener MC, Wallace TL, Kilduff TS (July 2019). "Trace amine-associated receptor 1 agonism promotes wakefulness without impairment of cognition in Cynomolgus macaques". Neuropsychopharmacology. 44 (8): 1485–1493. doi:10.1038/s41386-019-0386-8. PMC   6784974 . PMID   30954024.
  156. ↑ Raony Í, Domith I, Lourenco MV, Paes-de-Carvalho R, Pandolfo P (July 2022). "Trace amine-associated receptor 1 modulates motor hyperactivity, cognition, and anxiety-like behavior in an animal model of ADHD". Prog Neuropsychopharmacol Biol Psychiatry. 117: 110555. doi:10.1016/j.pnpbp.2022.110555. PMID   35346791.
  157. 1 2 Dedic N, Dworak H, Zeni C, Rutigliano G, Howes OD (December 2021). "Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies". Int J Mol Sci. 22 (24): 13185. doi: 10.3390/ijms222413185 . PMC   8704992 . PMID   34947997.
  158. 1 2 Liu JF, Li JX (2018). "TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg". Front Pharmacol. 9: 279. doi: 10.3389/fphar.2018.00279 . PMC   5881156 . PMID   29636691.
  159. 1 2 Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, Metzler V, Chaboz S, Groebke Zbinden K, Galley G, Norcross RD, Tuerck D, Bruns A, Morairty SR, Kilduff TS, Wallace TL, Risterucci C, Wettstein JG, Hoener MC (May 2013). "A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight". Mol Psychiatry. 18 (5): 543–556. doi:10.1038/mp.2012.57. PMID   22641180.
  160. ↑ Cotter R, Pei Y, Mus L, Harmeier A, Gainetdinov RR, Hoener MC, Canales JJ (2015). "The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects". Front Neurosci. 9: 39. doi: 10.3389/fnins.2015.00039 . PMC   4327507 . PMID   25762894.
  161. ↑ Begni V, Sanson A, Luoni A, Sensini F, Grayson B, Munni S, Neill JC, Riva MA (April 2021). "Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856". Int J Mol Sci. 22 (8): 4119. doi: 10.3390/ijms22084119 . PMC   8073823 . PMID   33923479.
  162. ↑ Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting Addiction"--The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. PMC   4724540 . PMID   26644139. [...] EPPTB's effect on the spontaneous locomotor activity in a familiar environment displayed by WT and taar1-deficient mice chronically exposed to 3 mg/kg METH (i.p.) over a range of doses was examined. The results of this study (Grandy, 2014; SfN abstracts) support the interpretation that EPPTB prevents to a significant degree METH-stimulated locomotor activity but only in WT mice with a history of chronic METH exposure.
  163. ↑ Grandy DK (16 November 2014). A G protein-coupled receptor mechanism of action distinguishes methamphetamine from cocaine. Neuroscience 2014. Retrieved 6 January 2025. The TAAR1-selective antagonist EPPTB blocked methamphetamine- and bupropion-stimulated chloride conductance in Xenopous oocytes co-expressing mouse TAAR1 and the human cystic fibrosis transmembrane conductance regulator in a concentration-dependent manner with IC50's of 2.3±0.3nM and 4.3±0.7nM, respectively. [...] EPPTB displayed no affinity for mouse biogenic amine transporters nor did it produce a significant phenotype in wildtype or taar1-/- mice. In contrast, at the highest dose tested (100 mg/kg, i.p.) EPPTB inhibited approximately 70% of methamphetamine-stimulated (3 mg/kg, i.p.) activity in wildtype mice while having no effect on similarly treated [TAAR1] knockout mice. Intraperitoneal co-administration of methamphetamine (3 mg/kg) and bupropion (50 mg/kg) to wildtype mice produced greater activity than either drug alone, an effect absent from [TAAR1] knockout mice. [...] The existence of a methamphetamine-activated G protein-coupled receptor that is also activated by bupropion [...]
  164. ↑ Dedic N, Jones PG, Hopkins SC, Lew R, Shao L, Campbell JE, Spear KL, Large TH, Campbell UC, Hanania T, Leahy E, Koblan KS (October 2019). "SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action". J Pharmacol Exp Ther. 371 (1): 1–14. doi:10.1124/jpet.119.260281. PMID   31371483.
  165. ↑ File SE, Tucker JC (1986). "Behavioral consequences of antidepressant treatment in rodents". Neurosci Biobehav Rev. 10 (2): 123–134. doi:10.1016/0149-7634(86)90023-0. PMID   3526203.
  166. ↑ Amato D, Pum ME, Groos D, Lauber AC, Huston JP, Carey RJ, de Souza Silva MA, Müller CP (August 2015). "Neuropharmacology of light-induced locomotor activation". Neuropharmacology. 95: 243–251. doi:10.1016/j.neuropharm.2015.03.023. PMID   25842246. It was found that visual stimulation of rats with white-light of 82 lux intensity induced locomotor activity and increased extracellular 5-HT and dopamine (DA) levels in the visual cortex (Müller et al., 2007a; Müller and Huston, 2007) and 5-HT in the medial prefrontal cortex (Pum et al., 2008). The 5-HT and DA increase were also seen in anesthetized animals (Pum et al., 2008). Cocaine, which induces serotonergic and dopaminergic activation (Izenwasser et al., 1990; Müller and Homberg, 2015), potentiates [light-induced locomotor activity (LIA)] (Pum et al., 2011).
  167. ↑ McCarson KE (2020). "Strategies for Behaviorally Phenotyping the Transgenic Mouse". Transgenic Mouse. Methods Mol Biol. Vol. 2066. pp. 171–194. doi:10.1007/978-1-4939-9837-1_15. ISBN   978-1-4939-9836-4. PMID   31512217.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.