Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepineeffects on food consumption and plus-maze learning behaviors in rats

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA (A)) receptor active neurosteroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one ( allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor an tagonistic neurosteroid, Delta 5-androsten-3 beta-ol-17-one sulfate (dehydr oepiandrosterone sulfate), on food intake and elevated plus-maze learning b ehaviors. Allopregnanolone (0.25 mg/kg, SC) and triazolam (0.25 mg/kg, IF) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/k g, SC) elicited an anorectic effect. However, allopregnanolone was more pot ent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following deh ydroepiandrosterone sulfate was alike in male and female rats. The triazola m- and allopregnanolone-induced hyperphagic effect was blocked by bicuculli ne (1 mg/kg, IF), a selective GABA(A) receptor antagonist. In contrast to t riazolam, the hyperphagic effect of allopregnanolone was insensitive to flu mazenil (5 mg/kg, IF), a benzodiazepine antagonist. Vehicle-treated diestro us rats displayed moderately higher latencies in the elevated plus-maze lea rning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in ma le and female rats, the magnitude of impairment-induced by triazolam was si gnificantly higher in diestrous females than proestrus females. Dehydroepia ndrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepi nes and neurosteroids may be sensitive to changes in anxiety, the different ial data suggest that neurosteroid-induced effects are at least partly spec ific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of neurosteroids and benzodiazepin es on food consumption and learning and memory processes. (C) 1998 Elsevier Science Inc.