Tetrad Test
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The tetrad test is a series of behavioral paradigms in which rodents treated with
cannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
such as THC show effects. It is widely used for screening drugs that induce cannabinoid receptor-mediated effects in rodents. The four behavioral components of the tetrad are spontaneous activity, catalepsy, hypothermia, and analgesia. Common assays for these behavioral paradigms are as follows: * Spontaneous activity (or
hypomotility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
) is determined by an
open field test 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 (usually rodents) in scientific research. However, the extent to which behavio ...
, in which a mouse is placed in a cage with perpendicular grid lines, usually spaced by approx. 1 inch. An experimenter counts the number of line crossings by the mouse in a given amount of time. * Catalepsy is determined by the bar test. The mouse is placed on a bar oriented parallel to and approximately 1 inch off of the ground. If the mouse remains immobile on the bar for typically more than 20 seconds, it is considered cataleptic. *
Hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe h ...
(reduced body temperature) is determined by using a rectal probe to measure the rectal temperature. * Analgesia is usually determined by the hot plate or tail immersion test. In the hot plate test, the mouse is placed on a heated plate, typically between 54 and 58°C. An experimenter measures the time it takes for the animal to raise its feet or jump off of the hot plate. In the tail immersion test, the mouse is immobilized and its tail is placed into a warm water bath, typically also between 54 and 58°C. An experimenter measures the time it takes for the mouse to remove its tail from the water bath. Direct CB1 agonists, such as THC (the psychoactive component of
marijuana Cannabis, also known as marijuana among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various tra ...
), or WIN 55,212-2, have effects in all components of the tetrad and induce hypomotility, catalepsy, hypothermia, and analgesia in rodents. Accordingly, all true "tetrad effects" are not observed following treatment with
antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
or
inverse agonists In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse ...
of CB1 such as
rimonabant Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in t ...
. Data have shown, that also CB2 receptors are involved in the tetrad effects induced by cannabinoids, and other, associated with CB1 agonism.


References

Behavioral concepts Cannabinoids Neuropsychology {{psych-stub