Progesterone withdrawal increases the anxiolytic actions of gaboxadol: Role of α4βδ GABA_A receptors

Hippocampal α4βδ GABA_A receptors (GABA_A-R) are increased following progesterone withdrawal (PWD) in a rodent model of premenstrual anxiety. This α4βδ receptor isoform uniquely responds to the GABA agonist gaboxadol (THIP) with a maximum current greater than that gated by GABA, and is potentiated more by pentobarbital than are other GABA_A-R. We therefore investigated the anxiolytic effects of these drugs using the elevated plus maze. Gaboxadol (1.25 mg/kg) was markedly more anxiolytic in animals undergoing PWD than in controls. Pentobarbital (10 mg/kg) also produced a greater anxiolytic effect during PWD. These results suggest that the pharmacological properties of α4βδ GABA_A-R following PWD are evident behaviorally. Alterations in the α4βδ GABA_A-R population may have implications for the etiology and treatment of premenstrual syndrome.