3-ALPHA-OH-DHP AND 5-ALPHA-THDOC IMPLANTS TO THE VENTRAL TEGMENTAL AREA FACILITATE SEXUAL RECEPTIVITY IN HAMSTERS AFTER PROGESTERONE PRIMING TO THE VENTRAL MEDIAL HYPOTHALAMUS

Progesterone (P) stimulation to both the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in female hamsters, despite the sparse population of estrogen-induced P receptors found in the VTA. Instead, P may act at neuronal membranes in the VTA. These P effects may be mediated by actions on the gamma-aminobutyric acid(A)- (GABA(A))-benzodiazepine receptor complex (GBR). Many progestin metabolites have a greater effect in vitro on benzodiazepine binding and Cl- flux than P. If P's actions are due to metabolism to a progestin more potent at the GBR, then applying one of those progestin metabolites directly to the VTA should facilitate receptivity, if coupled with P to the VMH. To test this hypothesis three P metabolites, in decreasing order of activity at cortical synaptosome GBR, were tested: 5alpha-pregnan-3alpha-ol-20-one (3alpha-OH-DHP), 5alpha-pregnan-3alpha,21-diol-20-one (5alpha-THDOC) and 5beta-pregnan-3alpha,21-diol-20-one (5beta-THDOC). Ovariectomized hamsters were implanted with chronic cannulae, one aimed above the VMH and the other over the contralateral VTA. Animals were estrogen-primed and tested for sexual receptivity 4 h after a P containing insert was applied to the VMH and a metabolite containing insert was applied to the VTA. The following week the contents of the tubes were reversed; on the third week P was applied to both sites. Facilitation of receptivity occurred only when P was applied to the VMH and either P or a metabolite was applied to the VTA. The reversed treatment was not effective. The progestin metabolites in order of behavioral effectiveness were: 3alpha-OH-DHP = 5alpha-THDOC >> 5beta-THDOC. This behavioral rank order is consistent with an action at the GBR.