Social interaction tests

Elevated plus-maze Social interaction test Light/dark shuttle-box... 

Most of these models evaluate the effects of drugs on the behaviour of animals when they are exposed to a novel environment. Novelty normally reduces animals exploratory activity but established anti-anxiety drugs consistently increase exploration of, and approaches to, the novel stimulus and reduce the neophobic ( avoidance ) reaction. There are several examples of tests based on this principle (Table 19.2) but two that are widely used are the plus-maze and the social interaction tests. 

Neurokinin receptors NK2 receptor agonists (e.g. GR64349) have an anxiogenic profile in animal models while the antagonists (GR100679) have an anti-anxiety effect. However, NKi receptor antagonists have also been reported to have antianxiety activity in the social interaction test (File 1997). 

File, SE (1997) Anxiolytic action of a neurokininl receptor antagonist in the social interaction test. Pharmacol. Biochem. Behav. 58 747-752. 

The disinhibitory effects of 5-HT3 receptor antagonists are now well documented [29, 30]. These compounds act to restore normal behaviour to animals in conditions which are mildly aversive, such as a novel brightly lit test area. Such effects may be predictive of anxiolytic activity. An example of such disinhibition is the effect of ondansetron in the rat social interaction test in which the level of interaction between two rats is measured under certain defined conditions [29]. In non-aversive conditions this type of behaviour is quite marked, but it is suppressed in novel highly illuminated conditions. Ondansetron overcomes this suppression, as do known anxiolytics such as diazepam. 

Nicotine in dorsal raphe Reversed withdrawal-induced anxiety (social interaction test) Cheeta et al. (2001)... 

Vale A, Green S, Montgomery AM, Shall S (1998) The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J Psychopharmacol 12 268-272 Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41 -residue ovine hypothalamic peptide that stimulates secretion of corticotropin and p-endorphin. Science 213 1394-1397... 

Rots NY, De Jong J, Workel JO, Levine S, Cools AR, De Kloet ER (1996) Neonatal maternally deprived rats have as adults elevated basal pituitary-adrenal activity and enhanced susceptibility to apomorphine. J Neuroendocrinol 8 501-506 Sajdyk T, Schober D, Smiley D, Gehlert D (2002b) Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala. Pharmacol Biochem Behav 71 419-423 Sajdyk TJ, Vandergriff MG, Gehlert DR (1999) Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. Eur J Pharmacol 368 143-147... 

Cheeta, S., Tucci, S., Sandhu, J., et al. Anxiolytic actions of the substance P (NK1) receptor antagonist L-760735 and the 5-HT1A agonist 8-OH-DPAT in the social interaction test in gerbils. Brain Res. 915, 170-175, 2001. 

Thus, the use of some strains should be avoided as their autism-like behavior may prevent the relevance of this test as a model of anxiety. In performing the social interaction test for screening anxiolytic and anxiogenic drugs, it is suggested that the same two mice are not re-introduced into the same environment together, as this may eliminate the social novelty of the condition, and will affect their test performance. 

Sams-Dodd E Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test. Behav. Pharmacol. 1997 8 196-215. Mansbach RS, Geyer MA Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat. Neuropsychopharmacology 1989 2 299-308. 

File, S. bl., Pellow, S., Brae.strup, C. (1985). Effects ofthc betacarboline, FG 7142 in the social interaction test of anxiety and the holeboard Correlations between behavior and plasma concentrations. Pharmacolojjy, Biochemistry, and Behavior, 22, 941-944. 

GV150013 has shown activity in a number of animal models of anxiety. In the mouse black/white box test GV150013 increased the time that naive mice remain in a brightly illuminated section of an activity box The effect was dose related and significant increases were measured at 0.1, 0.3 and l. Ong.kg 1.Similar anxiolytic effects were seen in the rat social interaction test and the marmoset human threat test [25]. The ED50 values are given in table 5. 

Two selective 5-HT4 receptor antagonists, SB 204070 (23) and SB 207266 (24), were determined to have modest anxiolytic activity in rats when evaluated in the social interaction test [62], Rats given either compound and subjected to the elevated-plus maze spent increased amounts of time in the open arms compared with controls. In another model of anxiety, the Gel-ler-Seifter conflict paradigm, neither compound had an effect on either punished or unpunished responding. These compounds had similar efficacy to chlordiazepoxide in the social interaction test, but were less efficacious in the elevated-plus maze. 

CA has been used for centuries in Ayurvedic medicine for psychoactive purposes to control anxiety and help in relaxation and mental calmness. Various studies and evaluations by human and animal models have confirmed the potential claim of CA and its triterpenoid centellosides in anxiolytic activity. In animal studies, the methanolic and ethyl acetate extract of CA as well as the AS of the plant have been reported to possess anxiolytic activity in rat behavioral models [51], In elevated plus maze study, CA methanol extract (3,047 mg kg of body weight) and AS (3 and 5 mg kg ) significantly reduced the number of closed arm entries and increased the time spent in protected head dips, whereas both CA ethyl acetate extract (111 mg kg ) and AS (3 and 5 mg kg ) significantly increased the number of protected head dips and the time spent for this activity. For the open-field test, AS (3-10 mg kg ) significantly increased the rat spent time (41.3 s) at the center of the arena, while the social interaction test treatment with 1 and 3 mg kg of AS significantly reduced the number of non-interaction activity by 29.8 s and 35.0 s, respectively. 

Kennett, G.A. (1992) 5-HTic receptor antagonists have anxiolytic-like actions in the rat social interaction test. Psychopharmacology, 107, 397-402. 

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