Contribution of GABA 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 GABA receptors in rodents causes behavioral deficits, including impaired attention and sociability, that are consistent with the symptoms of these conditions. The subunit composition of GABA receptors is diverse and can affect receptor function. The current experiment examined the role of GABA 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 GABA receptor inverse agonist), L-655,708 (0-1.0 mg/kg; a low efficacy inverse agonist at α-containing GABA receptors), MRK-016 (0.0-2.0 mg/kg; a high efficacy inverse agonist at α-containing GABA receptors), or L-838,417 (0.0-3.0 mg/kg; an antagonist at α-containing receptors and a partial agonist at α, α, α-containing GABA 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 GABA receptor signaling decreased sociability and attention, a result consistent with past research demonstrating cortical GABA receptor blockade impairs social behavior and attention. Overall, the effects of the receptor subtype selective ligands were minimal; α-containing GABA receptors may contribute to the attentional deficit but do not contribute to the decrease in sociability. Further research is needed to determine the GABA receptor subunits that contribute to social behavior and attention.