The hole-board test (HBT) is an experimental method used in scientific research to measure anxiety, stress, neophilia and emotionality in animals. [1] [2] [3] Because of its ability to measure multiple behaviors it is a popular test in behavioral pharmacology, but the results are controversial. [4]
The HBT was designed in the 1970s to mitigate the flaws of the open field test (OFT), another animal model that measures anxiety and exploratory behavior. Exploratory behavior requires a choice to be made to explore, but since the OFT is just simply a brightly lit area, the animal doesn't have a choice. The OFT also doesn't differentiate between locomotion and exploration. [5]
The HBT apparatus is an area with walls around it to prevent escape. The floor of the area is covered with holes. Over the years the HBT apparatus has become more complex. Modern devices are now monitored by computer and have infrared beams.
The three common activities are head dipping, rearing, and locomotion. Head dipping is commonly defined as when the animal puts his head into the hole until its ears are level with the floor or in modern devices when it breaks the infrared beam. Rearing is when the animal stands on its hind legs. Locomotion is the animal moving to a different area with all four paws. If the animal moves into the central area it is as separate observation because the central area is the most threatening to animals. These three behaviors are exploratory and the more they occur, the less anxious the animal is. On the other hand, if the animal doesn't show these behaviors, then it is more anxious. [5]
The procedure of this experiment can be modified depending on the behavior being measured. To examine anxiety a single animal is placed in the apparatus for five minutes where it is observed and then removed. Another animal that has been injected with an anxiolytic agent is then placed in the apparatus and then observed. Increased dose of anxiolytics leads to sedation. [1]
To observe neophilia and learning behavior, the test is typically done multiple times. [6] As the tests go on, the number of head dipping decreases because the animal has now gotten used to the arena. These tests can also have objects in the area to promote exploratory behaviors. Animals in areas with objects showed increased locomotion compared to animals in arenas without objects. [5]
Since the root cause of anxiety is idiopathic, animal models are difficult to create and therefore flawed. But because changes are seen through administration of anxiolytic agents, they are pharmacologically proven. The HBT studies show inconsistent results when administering known anti-anxiety medication such as benzodiazepines. [1]
The HBT showing neophilia is also controversial. Since animals show decreased head dipping, scientists conclude that it is a result of the animal becoming less fearful. However other studies have shown that after the amount of time with decreased head dipping, head dipping actually starts to increase, meaning that animals might have gotten bored with the area and are now exploring the holes. [5]
Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.
The behavioural despair test is a test, centered on a rodent's response to the threat of drowning, whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the effectiveness of antidepressants, although significant criticisms of its interpretation have been made.
An anxiogenic or panicogenic substance is one that causes anxiety. This effect is in contrast to anxiolytic agents, which inhibits anxiety. Together these categories of psychoactive compounds may be referred to as anxiotropic compounds.
DMCM is a drug from the β-carboline family that induces anxiety and convulsions by acting as a negative allosteric modulator of GABAA receptors — functionally opposite to benzodiazepines and related drugs which are positive allosteric modulators — and is used in scientific research for these properties to test new anxiolytic and anticonvulsant medications, respectively. It has also been shown to produce analgesic effects in animals, which is thought to be the drug's induced panic reducing the perception of pain.
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3-( ethynyl)pyridine (MTEP) is a research drug that was developed by Merck & Co. as a selective allosteric antagonist of the metabotropic glutamate receptor subtype mGluR5. Identified through structure-activity relationship studies on an older mGluR5 antagonist MPEP, MTEP has subsequently itself acted as a lead compound for newer and even more improved drugs.
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.
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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.
Jacqueline N. Crawley is an American behavioral neuroscientist and an expert on rodent behavioral analysis. Since July 2012, she is the Robert E. Chason Chair in Translational Research in the MIND Institute and professor of psychiatry and behavioral sciences at the University of California, Davis School of Medicine in Sacramento. Previously, from 1983–2012, she was chief of the Laboratory of Behavioral Neuroscience in the intramural program of the National Institute of Mental Health. Her translational research program focuses on testing hypotheses about the genetic causes of autism spectrum disorders and discovering treatments for the diagnostic symptoms of autism, using mouse models. She has published more than 275 peer-reviewed articles in scientific journals and 110 review articles and book chapters. According to Scopus, her works have been cited over 36,000 times, giving her an h-index of 99. She has co-edited 4 books and is the author of What's Wrong With my Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice, which was very well received.
The tail flick test is a test of the pain response in animals, similar to the hot plate test. It is used in basic pain research and to measure the effectiveness of analgesics, by observing the reaction to heat. It was first described by D'Amour and Smith in 1941.
The hot plate test is a test of the pain response in animals, similar to the tail flick test. Both hot plate and tail-flick methods are used generally for centrally acting analgesic, while peripherally acting drugs are ineffective in these tests but sensitive to acetic acid-induced writhing test.
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. These models provide insights into molecular, genetic, and epigenetic factors associated with depression. Criteria for valid animal models include face, construct, and predictive validity. Endophenotypes, such as anhedonia, behavioral despair, changes in appetite, neuroanatomical alterations, neuroendocrine disturbances, alterations in sleep architecture, and anxiety-related behaviors, are evaluated in these models. Antidepressant screening tests are employed to assess the effects of genetic, pharmacological, or environmental manipulations. Stress models, including learned helplessness, chronic mild stress, and social defeat stress, simulate the impact of stressors on depression. Early life stress models, psychostimulant withdrawal models, olfactory bulbectomy, and genetically engineered mice contribute to a comprehensive understanding of depression's etiology and potential therapeutic interventions.
Developed by Calvin S. Hall, the open field test is an experimental test used to assay general locomotor activity levels, anxiety, and willingness to explore in animals in scientific research. However, the extent to which behavior in the open field measures anxiety is controversial. The open field test can be used to assess memory by evaluating the ability of the animal to recognize a stimulus or object. Another animal test that is used to assess memory using that same concept is the novel object recognition test.
A preference test is an experiment in which animals are allowed free access to multiple environments which differ in one or more ways. Various aspects of the animal's behaviour can be measured with respect to the alternative environments, such as latency and frequency of entry, duration of time spent, range of activities observed, or relative consumption of a goal object in the environment. These measures can be recorded either by the experimenter or by motion detecting software. Strength of preference can be inferred by the magnitude of the difference in the response, but see "Advantages and disadvantages" below. Statistical testing is used to determine whether observed differences in such measures support the conclusion that preference or aversion has occurred. Prior to testing, the animals are usually given the opportunity to explore the environments to habituate and reduce the effects of novelty.
Marble burying is an animal model used in scientific research to depict anxiety or obsessive–compulsive disorder (OCD) behavior. It is based on the observation that rats and mice will bury either harmful or harmless objects in their bedding. While widely used there is significant controversy over the interpretation of its results.
The light-dark box test (LDB) is a popular animal model used in pharmacology to assay unconditioned anxiety responses in rodents. The extent to which behavior in the LDB measures anxiety is controversial.
The Vogel conflict test (VCT) is a conflict based experimental method primarily used in pharmacology. It is used to determine anxiolytic properties of drugs. The VCT predicts drugs that can manage generalized anxiety disorders and acute anxiety states.