Contribution of GABAA receptor subunits to attention and social behavior.

INTRODUCTION: GABA dysfunction is associated with a number of psychiatric conditions including schizophrenia, autism and depression. Blocking cortical GABAA receptors in rodents causes behavioral deficits, including impaired attention and sociability, that are consistent with the symptoms of these conditions. The subunit composition of GABAA receptors is diverse and can affect receptor function. The current experiment examined the role of GABAA receptors containing different α-subunits in social behavior and attention.
METHODS: Male Sprague-Dawley rats were administered FG7142 (0.0-5.0 mg/kg; a non-selective GABAA receptor inverse agonist), L-655,708 (0-1.0 mg/kg; a low efficacy inverse agonist at α5-containing GABAA receptors), MRK-016 (0.0-2.0 mg/kg; a high efficacy inverse agonist at α5-containing GABAA receptors), or L-838,417 (0.0-3.0 mg/kg; an antagonist at α1-containing receptors and a partial agonist at α2, α3, α5-containing GABAA receptors) and either tested on the social interaction and social preference tests or the 5-choice serial reaction time task.
RESULTS: FG7142 decreased social interactions and impaired attention. MRK-016 impaired attention but did not affect social behavior. Neither L-655,708 nor L-838,417 significantly affected either social behavior or attention. DISCUSSION: Systemic reduction in GABAA receptor signaling decreased sociability and attention, a result consistent with past research demonstrating cortical GABAA receptor blockade impairs social behavior and attention. Overall, the effects of the receptor subtype selective ligands were minimal; α5-containing GABAA receptors may contribute to the attentional deficit but do not contribute to the decrease in sociability. Further research is needed to determine the GABAA receptor subunits that contribute to social behavior and attention.