Hole-board test

Last updated

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]

Contents

Concept

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]

Scientific procedure

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]

Controversy

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]

See also

Related Research Articles

<span class="mw-page-title-main">Alpidem</span> Anxiolytic medication

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.

<span class="mw-page-title-main">Behavioural despair test</span>

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.

<span class="mw-page-title-main">Chlordiazepoxide</span> Benzodiazepine class sedative and hypnotic medication

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.

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

DMCM is a drug from the β-carboline family. It acts as a negative allosteric modulator of GABAA receptors, meaning that it causes the opposite effects to the benzodiazepine class of drugs. As such, DMCM has anxiogenic and convulsant properties, and is used in scientific research to induce anxiety so that new anxiolytic medications can be tested, and to produce convulsions so that anticonvulsant medications can be tested. It has also been shown to produce analgesic effects in animals, thought to be because it produces panic which reduces the perception of pain.

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

Benzoctamine is a drug that possesses sedative and anxiolytic properties. Marketed as Tacitin by Ciba-Geigy, it is different from most sedative drugs because in most clinical trials it does not produce respiratory depression, but actually stimulates the respiratory system. As a result, when compared to other sedative and anxiolytic drugs such as benzodiazepines like diazepam, it is a safer form of tranquilizing. However, when co-administered with other drugs that cause respiratory depression, like morphine, it can cause increased respiratory depression.

<span class="mw-page-title-main">Elevated plus maze</span> Scientific test for laboratory mice

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.

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

Zacopride is a potent antagonist at the 5-HT3 receptor and an agonist at the 5-HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the (R)-(+)-enantiomer being the more active form. It also has antiemetic and pro-respiratory effects, both reducing sleep apnea and reversing opioid-induced respiratory depression in animal studies. Early animal trials have also revealed that administration of zacopride can reduce preference for and consumption of ethanol.

<span class="mw-page-title-main">Conditioned place preference</span> Pavlovian conditioning

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. 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.

<span class="mw-page-title-main">Conflict procedure</span>

The conflict procedure is an experiment often used in scientific research to quantify anxiety levels by measuring changes in punished/unpunished responses. It is often used to screen drugs for their potential to inhibit anxiety.

<span class="mw-page-title-main">Osemozotan</span> Pharmaceutical drug

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.

<span class="mw-page-title-main">Jacqueline Crawley</span> American behavioral neuroscientist

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 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.

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 stimuli or object. Another animal test that is used to assess memory using that same concept is the novel object recognition test.

Spontaneous Alternation Behavior (SAB) describes the tendency to alternate in their pursuit of different stimuli in consecutive trials despite a lack of training or reinforcement. The Behavior emerged from experiments using animals, mainly rodents, who naturally demonstrated the behavioral pattern when placed in previously unexplored maze shapes.

<span class="mw-page-title-main">Preference test</span>

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.

<span class="mw-page-title-main">Marble burying</span> Animal model used in scientific research

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.

<span class="mw-page-title-main">Light-dark box test</span>

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.

References

  1. 1 2 3 Takeda, H.; Tsuji, M.; Matsumiya, T. (1998). "Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice". European Journal of Pharmacology. 350 (1): 21–29. doi:10.1016/S0014-2999(98)00223-4. PMID   9683010.
  2. Bilkei-Gorzó, A.; Gyertyán, I. (1996). "Some doubts about the basic concept of hole-board test". Neurobiology (Budapest, Hungary). 4 (4): 405–415. PMID   9200132.
  3. File and Wardill, 1975a; Ljungberg and Ungerstedt, 1976
  4. Pharmacological and genetic influences on hole-board behaviors in mice. Kliethermes CL, Crabbe JC Pharmacol Biochem Behav. 2006 Sep; 85(1):57-65. [PubMed]
  5. 1 2 3 4 Brown, Gillian R; Nemes, C (2008). "The exploratory behaviour of rats in the hole-board apparatus: Is head-dipping a valid measure of neophilia?". Behavioural Processes. 78 (3): 442–448. doi:10.1016/j.beproc.2008.02.019. PMC   2396234 . PMID   18406075.
  6. d'Isa, R.; Comi, G.; Leocani, L. (2021). "The 4-Hole-Board Test for Assessment of Long-Term Spatial Memory in Mice". Current Protocols. 1 (8): e228. doi:10.1002/cpz1.228. PMID   34432376. S2CID   237294883.