Behavioral effects of 3a-androstanediol II: Hypothalamic and preoptic area actions via a GABAergic mechanism

摘要: We investigated whether 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol; 3 alpha-Diol), a neurosteroid whose effects are primarily inhibitory to sexual behavior, may act through interactions with gamma-aminobutyric acid (GABA) receptor complexes (GBRs) in the medial basal hypothalamus (MBH) and preoptic area (POA). In Experiment (Exp.) 1, ovariectomized (ovx) rats were implanted bilateral guide cannulae aimed above MBH later treated beta-estradiol (E2, 2 injections of 1 microgram/0.2 ml 10% ethanol) either alpha-Diol (3.0 mg/kg, s.c.) or vehicle. Progesterone (0.5 mg, was given 24 h after first E2 injection pre-test for lordosis responsiveness carried out 4 later. The GABAA agonist, muscimol (50 ng), then infused into tested 10, 30 60 min Muscimol infusion facilitated behavior vehicle-treated controls, but alpha-Diol-treated animals failed show this facilitation. To ascertain would also prevent muscimol's action POA, site which inhibits, rather than facilitates, receptivity, ovx Exp.2 POA E2, alpha-Diol, P as Exp. 1. each significantly inhibited receptivity; when they combined, inhibition more pronounced. 3, infusions antagonist, bicuculline, counteracted alpha-Diol's behavior. 4, vitro treatment membrane fractions (30 microM) enhanced maximal [3H]muscimol binding without altering affinity sites agonist. These data suggest that inhibits progestin-induced via actions at GBR both POA.