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Conditioned compensatory response (CR) is an automatic response that is opposite to the effect of alcohol or substance usage. Conditioned behavior is a key part of substance addiction. [1] This response has many implications. For instance, a drug user will be most tolerant to the drug in the presence of cues that have been associated with it, because such cues elicit compensatory responses. As a result, overdose is usually not due to an increase in dosage, but due to taking the drug in a new place without familiar cues, which would have otherwise allowed the user to tolerate the drug. CR includes a heightened pain sensitivity, and decreased body temperature, and might cause discomfort, thus motivating the drug user to continue usage of the drug. This is one of several ways classical conditioning might be a factor in drug addiction and dependence. [2]
In a classic experiment, Shepard Siegel conditioned rats with morphine. Later the rats were exposed to the same environmental stimuli that had been associated with morphine but did not receive the drug. The CR was opposite to the effects of morphine, and the rats experienced hyperalgesia. Siegel suggested that compensatory CRs allow the organism to maintain a normal physiological state despite the administration of a drug and that they help to explain tolerance to drugs. The conditioned compensatory response may take place only in the case of subconscious learning, as the effects of conscious expectancies may tend to be in the direction of the expectation. Therefore, conditioning may lead either to a placebo analgesic response to morphine or a compensatory response. [3]
Dextromethorphan, or DXM, a common active ingredient found in many over-the-counter cough suppressant cold medicines, is used as a recreational drug and entheogen for its dissociative effects. Street names include Brownies, Dextro, Drix, Gel, Groove, Lean, Mega-perls, Poor man's ecstasy, Poor man's PCP, Red devils, Robo, Rojo, Rome, Skittles, Sizzurp, Triple Cs, Sky and Velvet.
Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the dried latex of the opium poppy; it is mainly used as a recreational drug for its euphoric effects. Heroin is used medically in several countries to relieve pain, such as during childbirth or a heart attack, as well as in opioid replacement therapy. Medical-grade diamorphine is used as a pure hydrochloride salt. Various white and brown powders sold illegally around the world as heroin are routinely diluted with cutting agents. Black tar heroin is a variable admixture of morphine derivatives—predominantly 6-MAM (6-monoacetylmorphine), which is the result of crude acetylation during clandestine production of street heroin.
Operant conditioning, also called instrumental conditioning, is a learning process where voluntary behaviors are modified by association with the addition of reward or aversive stimuli. The frequency or duration of the behavior may increase through reinforcement or decrease through punishment or extinction.
A placebo is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.
Classical conditioning is a behavioral procedure in which a biologically potent stimulus is paired with a neutral stimulus. The term classical conditioning refers to the process of an automatic, conditioned response that is paired with a specific stimulus.
The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.
Motivational salience is a cognitive process and a form of attention that motivates or propels an individual's behavior towards or away from a particular object, perceived event or outcome. Motivational salience regulates the intensity of behaviors that facilitate the attainment of a particular goal, the amount of time and energy that an individual is willing to expend to attain a particular goal, and the amount of risk that an individual is willing to accept while working to attain a particular goal.
Rat Park was a series of studies into drug addiction conducted in the late 1970s and published between 1978 and 1981 by Canadian psychologist Bruce K. Alexander and his colleagues at Simon Fraser University in British Columbia, Canada.
In internal medicine, relapse or recidivism is a recurrence of a past condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or recrudescence.
Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.
State-dependent memory or state-dependent learning is the phenomenon where people remember more information if their physical or mental state is the same at time of encoding and time of recall. State-dependent memory is heavily researched in regards to its employment both in regards to synthetic states of consciousness as well as organic states of consciousness such as mood. While state-dependent memory may seem rather similar to context-dependent memory, context-dependent memory involves an individual's external environment and conditions while state-dependent memory applies to the individual's internal conditions.
Cue reactivity is a type of learned response which is observed in individuals with an addiction and involves significant physiological and psychological reactions to presentations of drug-related stimuli. The central tenet of cue reactivity is that cues previously predicting receipt of drug reward under certain conditions can evoke stimulus associated responses such as urges to use drugs. In other words, learned cues can signal drug reward, in that cues previously associated with drug use can elicit cue-reactivity such as arousal, anticipation, and changes in behavioral motivation. Responses to a drug cue can be physiological, behavioral, or symbolic expressive. The clinical utility of cue reactivity is based on the conceptualization that drug cues elicit craving which is a critical factor in the maintenance and relapse to drug use. Additionally, cue reactivity allows for the development of testable hypotheses grounded in established theories of human behavior. Therefore, researchers have leveraged the cue reactivity paradigm to study addiction, antecedents of relapse, and craving, translate pre-clinical findings to clinical samples, and contribute to the development of new treatment methods. Testing cue reactivity in human samples involves exposing individuals with a substance use disorder to drug-related cues and drug neutral cues, and then measuring their reactions by assessing changes in self-reported drug craving and physiological responses.
The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.The reward system motivates animals to approach stimuli or engage in behaviour that increases fitness. Survival for most animal species depends upon maximizing contact with beneficial stimuli and minimizing contact with harmful stimuli. Reward cognition serves to increase the likelihood of survival and reproduction by causing associative learning, eliciting approach and consummatory behavior, and triggering positively-valenced emotions. Thus, reward is a mechanism that evolved to help increase the adaptive fitness of animals. In drug addiction, certain substances over-activate the reward circuit, leading to compulsive substance-seeking behavior resulting from synaptic plasticity in the circuit.
SB-277,011A is a drug which acts as a potent and selective dopamine D3 receptor antagonist, which is around 80–100 times selective for D3 over D2, and lacks any partial agonist activity.
Psychological dependence is a cognitive disorder and a form of dependence that is characterized by emotional–motivational withdrawal symptoms upon cessation of prolonged drug use or certain repetitive behaviors. Consistent and frequent exposure to particular substances or behaviors is responsible for inducing psychological dependence, requiring ongoing engagement to prevent the onset of an unpleasant withdrawal syndrome driven by negative reinforcement. Neuronal counter-adaptation is believed to contribute to the generation of withdrawal symptoms through changes in neurotransmitter activity or altered receptor expression. Environmental enrichment and physical activity have been shown to attenuate withdrawal symptoms.
Desomorphine is a semi-synthetic opioid commercialized by Roche, with powerful, fast-acting effects, such as sedation and analgesia. It was first discovered and patented in Germany by a German team working for Knoll in 1920 but was not generally recognized. It was later synthesized in 1932 by American chemist Lyndon Frederick Small. Small also successfully patented it in 1934 in the United States. Desomorphine was used in Germany, Austria, and Switzerland under the brand name Permonid and was described as having a fast onset and a short duration of action, with relatively little nausea compared to equivalent doses of morphine. Dose for dose it is roughly ten times more potent than morphine, with 1 mg desomorphine being equivalent 10 mg morphine, via the intravenous (IV) or intramuscular (IM) routes.
Conditioned place preference (CPP) is a form of Pavlovian conditioning used to measure the motivational effects of objects or experiences. This motivation comes from the pleasurable aspect of the experience, so that the brain can be reminded of the context that surrounded the "encounter". By measuring the amount of time an animal spends in an area that has been associated with a stimulus, researchers can infer the animal's liking for the stimulus. This paradigm can also be used to measure conditioned place aversion with an identical procedure involving aversive stimuli instead. Both procedures usually involve mice or rats as subjects. This procedure can be used to measure extinction and reinstatement of the conditioned stimulus. Certain drugs are used in this paradigm to measure their reinforcing properties. Two different methods are used to choose the compartments to be conditioned, and these are biased vs. unbiased. The biased method allows the animal to explore the apparatus, and the compartment they least prefer is the one that the drug is administered in and the one they most prefer is the one where the vehicle is injected. This method allows the animal to choose the compartment they get the drug and vehicle. In comparison, the unbiased method does not allow the animal to choose what compartment they get the drug and vehicle in. Instead, the researcher chooses the compartments.
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in the development of addiction.
BP-897 is a drug used in scientific research which acts as a potent selective dopamine D3 receptor partial agonist with an in vitro intrinsic activity of ~0.6 and ~70x greater affinity for D3 over D2 receptors and is suspected to have partial agonist or antagonist activity in vivo. It has mainly been used in the study of treatments for cocaine addiction. A study comparing BP-897 with the potent, antagonistic, and highly D3 selective SB-277,011-A found, "SB 277011-A (1–10 mg/kg) was able to block cue-induced reinstatement of nicotine-seeking, indicating that DRD3 selective antagonism may be an effective approach to prevent relapse for nicotine. In contrast, BP 897 did not block the cue-induced reinstatement of nicotine-seeking or nicotine-taking under the FR5 schedule."