Infusions of Diazepam and Allopregnanolone into the Midbrain Central Gray Facilitate Open-Field Behavior and Sexual Receptivity in Female Rats

Abstract

We have previously shown that blocking GABAA receptors with bicuculline in the dorsal and lateral quadrants of the rostral two-thirds of the midbrain central gray (MCG) in rats reduces the lordosis quotient (LQ) and proceptive behaviors without increasing the defensive index (McCarthy, Pfaff, and Schwartz-Giblin, 1991b), indicating that tonic release of endogenous GABA in the MCG has a primary facilitatory effect on reproductive behaviors. The present study tests whether two modulators of the GABAA-benzodiazepine-receptor complex, diazepam and the progesterone metabolite, allopregnanolone, facilitate female receptivity as well as open-field behavior. Ovariectomized estradiol benzoate (EB)-treated rats were bilaterally infused in the MCG with vehicle, diazepam, or allopregnanolone and tested 20 min after diazepam and 12 min after allopregnanolone. Animals were tested once each for both receptive or open-field behavior with testing sessions being at least 1 week apart in a crossover design between vehicle and one of the two drugs. Both diazepam and allopregnanolone significantly increased the lordosis quotient in a dose-dependent manner, the lowest effective dose tested being 100 and 250 ng, respectively. In the open-field test, infusion of diazepam (100 ng) in EB-treated rats significantly increased the ratio of central squares entered to total squares entered (C/T) without a change in total activity. Rats without EB elicited comparable C/T ratios when tested with five times as much diazepam. Diazepam infusions at more dorsal sites in the midbrain and in overlying cortex were without effect on C/T ratios in EB-treated rats. Allopregnanolone (500 ng) infusions in MCG of EB-treated rats did not alter C/T ratios compared to animals without EB. Our results are consistent with diazepam and allopregnanolone acting through the GABAA receptors of the MCG to enhance female sexual receptivity and with estradiol potentiating the effect of diazepam in the MCG to increase openfield behavior.