Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability

Introduction: Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. Methods: Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0.5 mu l bicuculline methiodide (BMI, a GABA(A) receptor antagonist) at doses of 0, 25, or 50 ng/l. Rats were tested in the social interaction test, the social preference test, the sucrose preference test and for locomotor activity (BLA infusions only). Results: Intra-BLA or PFC BMI infusions decreased the amount of time and the number of social interactions in the social interaction test. Further, in the social preference test, rats infused with 50 ng BMI no longer exhibited a preference to explore a social over a non-social stimulus. The change in sociability was not due to a change in reward processing or locomotor behavior. Discussion: Decreasing GABA transmission in either the medial PFC or BLA decreased sociability. Thus, changes in GABA signaling observed in conditions such as autism or schizophrenia may mediate the social withdrawal characteristic of these conditions. Moreover, they suggest that social withdrawal may be treated by drugs that potentiate GABA transmission. (C) 2016 Elsevier B.V. All rights reserved.