Two animals, typically rats or mice, are placed into an arena and their interactions, for example, investigation, following, and grooming, are recorded for a period of time, usually 5 to 10 min. Social behaviors such as following, adjacent lying, and anogenital sniffing are recorded by an observer or via automated image analysis. Many drugs modulate behavior on the social interaction test: benzodiazepines, MDMA, and oxytocin tend to increase social interaction while amphetamines, cannabinoids, NMDA antagonists, and withdrawal from various
► drugs of abuse tend to decrease social interaction. In the high-light version of the then test, the arena is brightly illuminated and this creates an aversive situation for the animals, which results in low levels of social interaction. In this configuration, it is possible to identify drugs or manipulations that reduce the inferred level of anxiety in the animals, that is, they result in an increased level of social interaction. In the low-light version, the arena is only illuminated with low, typically red light in order to minimize aversive cues. In this configuration, the level of interaction will be maximal and it is possible to test drugs or manipulations that reduce the normal level of social interactions. In addition to light level, which is the strongest experimental factor, the animals' familiarity with the arena can be varied, for example, by having been introduced to the arena prior to the testing session, and whether the animals know each other prior to the testing session. Familiarity with the arena will reduce the level of aversive cues, but will also increase the level of territorial behavior, resulting in more fighting between the animals. Familiarity between the animals being tested can reduce the level of aversive cues during the testing situation and the level of fighting, because a hierarchy does not have to be established, but it may also increase variability in the data, because the animals will have a preestablished rank that not will be present if they are unfamiliar to each other.
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