INFUSIONS OF DIAZEPAM AND ALLOPREGNANOLONE INTO THE MIDBRAIN CENTRAL GRAY FACILITATE OPEN-FIELD BEHAVIOR AND SEXUAL RECEPTIVITY IN FEMALE RATS

We have previously shown that blocking GABA(A) receptors with bicucull ine in the dorsal and lateral quadrants of the rostral two-thirds of t he midbrain central gray (MCG) in rats reduces the lordosis quotient ( LQ) and preceptive behaviors without increasing the defensive index (M cCarthy, Pfaff, and Schwartz-Giblin, 1991b), indicating that tonic rel ease of endogenous GABA in the MCG has a primary facilitatory effect o n reproductive behaviors. The present study tests whether two modulato rs of the GABA(A)-benzodiazepine-receptor complex, diazepam and the pr ogesterone 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, diaze pam, or allopregnanolone and tested 20 min after diazepam and 12 min a fter allopregnanolone. Animals were tested once each for both receptiv e or open-field behavior with testing sessions being at least 1 week a part in a crossover design between vehicle and one of the two drugs. B oth 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 ra tio of central squares entered to total squares entered (C/T) without a change in total activity. Rats without EB elicited comparable C/T ra tios when tested with five times as much diazepam. Diazepam infusions at more dorsal sites in the midbrain and in overlying cortex were with out 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 a llopregnanolone acting through the GABA(A) receptors of the MCG to enh ance female sexual receptivity and with estradiol potentiating the eff ect of diazepam in the MCG to increase open-field behavior. (C) 1995 A cademic Press, Inc.