Anti-conflict-like actions of intralateral septal infusions of allopregnanolone in Wistar rats

Abstract

The aim of the present study was to test the hypothesis that allopregnanolone infused into the lateral septal nuclei will reduce conflict-like behavior in ovariectomized rats. The interaction with systemic administration of several agonists and antagonists of the GABA-A receptor was assessed. Results showed that intralateral septal doses of allopregnanolone (1.0 μg, P<.05; 2.0 μg, P<.05) or systemic injections of allopregnanolone (1.0 mg/kg sc, P<.05; 2.0 mg/kg sc, P<.05), diazepam (2.0 mg/kg ip, P<.05), or muscimol (0.3 mg/kg ip, P<.05; 0.6 mg/kg ip, P<.05) reduced conflict-like behavior. Subthreshold doses of intralateral septal infusions of allopregnanolone (0.5 μg/side) synergized with systemic subthreshold doses of GABA-A agonists: allopregnanolone (0.5 mg/kg, P<.05), diazepam (1.5 mg/kg, P<.05), or muscimol (0.1 mg/kg, P<.05). The GABA-A antagonists, flumazenil (0.1 mg/kg ip) and bicuculline (2.0 mg/kg ip) attenuated the synergism between intralateral septal infusions of allopregnanolone and diazepam or muscimol, respectively. Conversely, neither flumazenil ( P<.05) nor bicuculline ( P<.05) attenuated the synergism of the combination allopregnanolone (intralateral septum nuclei; 0.5 μg/side) plus systemic injections of allopregnanolone. In conclusion, allopregnanolone reduced conflict-like behavior probably acting at the GABA-A receptors found in the lateral septal nuclei.