Progesterone withdrawal increases the anxiolytic actions of gaboxadol: role of alpha4betadelta GABAA receptors.

摘要

Hippocampal alpha4betadelta GABA receptors (GABA -R) are increased following progesterone withdrawal (PWD) in a rodent model of premenstrual anxiety. This alpha4betadelta 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 -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 alpha4betadelta GABA -R following PWD are evident behaviorally. Alterations in the alpha4betadelta GABA -R population may have implications for the etiology and treatment of premenstrual syndrome.(A) (A) (A) (A) (A)