The rotarod performance test is a performance test based on a rotating rod with forced motor activity being applied, usually by a rodent. The test measures parameters such as riding time (seconds) or endurance. Some of the functions of the test include evaluating balance, grip strength and motor coordination of the subjects; especially in testing the effect of experimental drugs [1] or after traumatic brain injury. [2]
In the test, a rodent is placed on a horizontally oriented, rotating cylinder (rod) suspended above a cage floor, which is low enough not to injure the animal, but high enough to induce avoidance of fall. Rodents naturally try to stay on the rotating cylinder, or rotarod, and avoid falling to the ground. The length of time that a given animal stays on this rotating rod is a measure of their balance, coordination, physical condition, and motor-planning. The speed of the rotarod is mechanically driven, and may either be held constant, or accelerated. [3]
A human analog to rotarod test might be treadmill running. Hamster, gerbil, and mouse owners can observe the principle in action when an animal climbs on the outside of its wheel, instead of inside of it. In the rotarod test, however, the rotation of the cylinder in experiments is mechanically driven.
The advantage of this test is that it creates a discretely measurable, continuous variable (length of time) that can be used for statistical purposes to quantify the effects of different drugs, conditions, and procedures. This test does not use subjective judgments of ability, and inter-rater reliability will be virtually perfect. Inter-laboratory reliability will only be achieved if the various parameters (size of cylinder, speed of cylinder, composition material of surface, and amount of practice/training given the animal) are also replicated. [4] The experiment is also very replicable from lab to lab (ibid). Moreover, these parameters may be adjusted variously to optimize the statistical separation of different conditions. For instance, alcohol effects on mice become less apparent when the speed is increased. [5]
Because of concern for impairment in human motor behavior from the use of prescription medications, the rotarod test is frequently used in early stages of drug development [6] to screen out drugs that might later cause subtle impairments, which might not be detected epidemiologically in a human population for a very long time. The test may be useful as a sensitive indicator of trauma induced by brain injury to laboratory rats. [7] Alcohol markedly impairs mouse performance in the rotarod test. [8] Research using the rotarod test with various chemical agonists and antagonists may help scientists determine which components of neurons mediate the effects of chemicals. [9] Testing of genetic knockout animals may help determine the genes most responsible for maintaining mammalian balance and coordination. [10] Comparing the performance of different animals with specific brain lesions helps scientists map which structures are critical for maintaining balance. [11]
Dizocilpine (INN), also known as MK-801, is a noncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore-blocker ketamine is used instead as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used non-competitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
An induced coma, also known as a medically induced coma, a barbiturate-induced coma, or a barb coma, is a temporary coma brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental. Barbiturate comas are used to protect the brain during major neurosurgery, as a last line of treatment in certain cases of status epilepticus that have not responded to other treatments, and in refractory intracranial hypertension following traumatic brain injury.
Quazepam is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is indicated for the treatment of insomnia including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.
The Barnes maze is a tool used in psychological laboratory experiments to measure spatial learning and memory. The test was first developed by Dr. Carol Barnes in 1979. The test subjects are usually rodents such as mice or lab rats, which either serve as a control or may have some genetic variable or deficiency present in them which will cause them to react to the maze differently. The basic function of Barnes maze is to measure the ability of a mouse to learn and remember the location of a target zone using a configuration of distal visual cues located around the testing area. This noninvasive task is useful for evaluating novel chemical entities for their effects on cognition as well as identifying cognitive deficits in transgenic strains of rodents that model for disease such as Alzheimer's disease. It is also used by neuroscientists to determine whether there is a causative effect after mild traumatic brain injury on learning deficits and spatial memory retention (probe) at acute and chronic time points. This task is dependent on the intrinsic inclination of the subjects to escape from an aversive environment and on hippocampal-dependent spatial reference memory.
Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs.
Prostaglandin E2 receptor 1 (EP1) is a 42kDa prostaglandin receptor encoded by the PTGER1 gene. EP1 is one of four identified EP receptors, EP1, EP2, EP3, and EP4 which bind with and mediate cellular responses principally to prostaglandin E2) (PGE2) and also but generally with lesser affinity and responsiveness to certain other prostanoids (see Prostaglandin receptors). Animal model studies have implicated EP1 in various physiological and pathological responses. However, key differences in the distribution of EP1 between these test animals and humans as well as other complicating issues make it difficult to establish the function(s) of this receptor in human health and disease.
The elevated plus maze (EPM) is a test measuring anxiety in laboratory animals that usually uses rodents as a screening test for putative anxiolytic or anxiogenic compounds and as a general research tool in neurobiological anxiety research such as PTSD and TBI. The model is based on the test animal's aversion to open spaces and tendency to be thigmotaxic. In the EPM, this anxiety is expressed by the animal spending more time in the enclosed arms.
Environmental enrichment is the stimulation of the brain by its physical and social surroundings. Brains in richer, more stimulating environments have higher rates of synaptogenesis and more complex dendrite arbors, leading to increased brain activity. This effect takes place primarily during neurodevelopment, but also during adulthood to a lesser degree. With extra synapses there is also increased synapse activity, leading to an increased size and number of glial energy-support cells. Environmental enrichment also enhances capillary vasculation, providing the neurons and glial cells with extra energy. The neuropil expands, thickening the cortex. Research on rodent brains suggests that environmental enrichment may also lead to an increased rate of neurogenesis.
Conditioned place preference (CPP) is a form of Pavlovian conditioning used to measure the motivational effects of objects or experiences. 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. In comparison, the unbiased method does not allow the animal to choose what compartment they get the drug and vehicle in and instead the researcher chooses the compartments.
Scrambler is a spontaneous mouse mutant lacking a functional DAB1 gene, resulting in a phenotype resembling that seen in the reeler mouse. The strain was first described by Sweet et al. in 1996.
Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor. Osemozotan has antidepressant, anxiolytic, antiobsessional, serenic, and analgesic effects in animal studies, and is used to investigate the role of 5-HT1A receptors in modulating the release of dopamine and serotonin in the brain, and their involvement in addiction to abused stimulants such as cocaine and methamphetamine.
Animal models of depression are research tools used to investigate depression and action of antidepressants as a simulation to investigate the symptomatology and pathophysiology of depressive illness or used to screen novel antidepressants.
SHIRPA is a standardized set of experimental procedures used by scientists to characterize the phenotype of genetically modified laboratory mice. The protocols are designed to test muscle function, cerebellar function, sensory function and neuropsychiatric function.
A nociception assay evaluates the ability of an animal, usually a rodent, to detect a noxious stimulus such as the feeling of pain, caused by stimulation of nociceptors. These assays measure the existence of pain through behaviors such as withdrawal, licking, immobility, and vocalization. The sensation of pain is not a unitary concept; therefore, a researcher must be conscious as to which nociception assay to use.
Research into the mental disorder of schizophrenia, involves multiple animal models as a tool, including in the preclinical stage of drug development.
7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves. It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF). 7,8-DHF is both orally bioavailable and able to penetrate the blood–brain barrier. A prodrug of 7,8-DHF with greatly improved potency and pharmacokinetics, R13, is under development for the treatment of Alzheimer's disease.
Manoj Kumar Jaiswal is an Indian neuroscientist. He is the full-time faculty (Instructor) in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai.
Mibampator is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which was under development by Eli Lilly for the treatment of agitation/aggression in Alzheimer's disease but was never marketed. It reached phase II clinical trials prior to the discontinuation of its development.
Tulrampator is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which is under development by RespireRx Pharmaceuticals and Servier for the treatment of major depressive disorder, Alzheimer's disease, dementia, and mild cognitive impairment. As of 2016, it is in phase II clinical trials for depression and Alzheimer's disease and phase I trials for dementia and mild cognitive impairment.
Douglas Leon Wahlsten is a Canadian neuroscientist, psychologist, and behavior geneticist. He is a professor emeritus of psychology at the University of Alberta. As of 2011, he was also a visiting professor at the University of North Carolina at Greensboro in North Carolina, United States. He is known for his laboratory research on the behavior of mice, and for his theoretical writings on a wide range of other topics. His laboratory research has included studies of the effects of different laboratory environments and experimenter characteristics on the results of mouse studies. He and his colleagues have also developed an altered form of the rotarod performance test involving wrapping sandpaper around the rod, to reduce the ability of mice to grip the rod and ride around on it. He has criticized some of his fellow behavior geneticists for trying to separate the effects of genes and the environment on human intelligence, an endeavor he considers futile. He also met and became friends with Leilani Muir, later helping to edit her autobiography, A Whisper Past. He was the president of the International Behavioural and Neural Genetics Society from 2000 to 2001.