MUSCIMOL FACILITATES SEXUAL RECEPTIVITY IN HAMSTERS WHEN INFUSED INTO THE VENTRAL TEGMENTUM

Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABA(A) receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10-mu-g estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100-mu-g progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5-mu-l. Control animals received 0.5-mu-l vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABA(A) receptor complex awaits further study.