GABAA receptors in the ventral tegmental area control the outcome of a social competition in rats

Social dominance can be attained through social competitions. Recent work in both humans and rodents has identified trait anxiety as a crucial predictor of social competitiveness. In addition, the anxiolytic GABA_A positive modulator, diazepam, injected either systemically or into the ventral tegmental area (VTA) was shown to increase social dominance. Here, we investigated the impact of pharmacologically targeting GABA_A receptors in the VTA for the outcome of a social competition between two unfamiliar male rats, one of them infused with vehicle and the Other one with the drug under study. We show that infusion of the GABA_A receptor agonist, muscimol, reduced anxiety-like behaviors and enhanced social competition, the GABA_A receptor antagonist, bicuculline had the opposite effects. Importantly, intra-VTA muscimol administration also counteracted the disadvantage of high anxious rats to win a social competition against low anxious rats. Furthermore, we assessed the effectiveness of targeting specific GABA_A receptor subunits by infusing zolpidem (α1-subunit agonist) or TCS1105 (a benzodiazepine ligand with α2-subunit agonistic and α1-subunit antagonistic effects) into the VTA. While zolpidem infusion did not affect the outcome of the social competition, TCS1105 enhanced social dominance. Our data highlight GABAergic mechanisms involving the engagement of α2-subunit containing GABA_A receptors in the VTA in the attainment of dominance rank. The involvement of α2-subunit containing GABA_A receptors in the VTA in the regulation of social competitiveness supports the potential therapeutic relevance of targeting these receptors to ameliorate anxiety-related social dysfunctions.