Contribution of GABA_A receptor subunits to attention and social behavior

GABA dysfunction is associated with a number of psychiatric conditions including schizophrenia, autism and depression. Blocking cortical GABA_A 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_A receptors is diverse and can affect receptor function. The current experiment examined the role of GABA_A receptors containing different α-subunits in social behavior and attention.

Male Sprague-Dawley rats were administered FG7142 (0.0-5.0 mg/kg; a non-selective GABA_A receptor inverse agonist), L-655,708 (0-1.0 mg/kg; a low efficacy inverse agonist at α₅-containing GABA_A receptors), MRK-016 (0.0-2.0 mg/kg; a high efficacy inverse agonist at α₅-containing GABA_A 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 GABA_A receptors) and either tested on the social interaction and social preference tests or the 5-choice serial reaction time task.

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.

Systemic reduction in GABA_A receptor signaling decreased sociability and attention, a result consistent with past research demonstrating cortical GABA_A receptor blockade impairs social behavior and attention. Overall, the effects of the receptor subtype selective ligands were minimal; α₅-containing GABA_A receptors may contribute to the attentional deficit but do not contribute to the decrease in sociability. Further research is needed to determine the GABA_A receptor subunits that contribute to social behavior and attention.