Social approach-avoidance behavior of a high-anxiety strain of rats: effects of benzodiazepine receptor ligands

Rational: To better understand anxiety disorders with social impairments as well as to identify new treatments, it is important to develop preclinical procedures involving social components of anxiety. Recently, a novel procedure was reported: the rat Social Approach-Avoidance (SAA) test. In this test, the time spent by a test rat in a large social compartment containing an unfamiliar stimulus rat reflects the anxiety state of the animal. It was shown that prestressing the test rat increased the avoidance of the social compartment as characterized by an increase in the time spent in the nonsocial compartment. Objective: (1) To use a high-anxiety strain, F-344 rats, instead of prestressed animals, (2) to automate the test by using video tracking to measure time spent in both compartments and their subdivisions, and (3) to validate this modified test with known benzodiazepine receptor ligands. Materials and methods: F-344 rats were treated with either chlordiazepoxide or diazepam (benzodiazepine receptor agonists), or RO 19-4603 or FG 7142 (benzodiazepine receptor inverse agonists). Results: The agonists produced anxiolytic-like effects, whereas the inverse agonists produced anxiogenic-like effects. These effects were most marked in the two extreme zones in terms of distance to the stimulus rat. Conclusions: F-344 rats display spontaneous avoidance behavior in the modified SAA procedure, and approach-avoidance behavior in these rats is sensitive to benzodiazepine agonists and inverse agonists in a bidirectional manner. The finding that the assessment of time spent into two virtual zones in each of the compartments markedly increased the sensitivity to both anxiolytics and anxiogenics will be discussed using the concept of physical defensive distance.