Progestins’ Rapid Facilitation of Lordosis When Applied to the Ventral Tegmentum Corresponds to Efficacy at Enhancing GABAAReceptor Activity

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Abstract
Progestins may have actions in the midbrain though γ-aminobutyric acid (GABA)A/benzodiazepine receptor complexes (GBRs) that are relevant for sexual receptivity. The efficacy and time course of various progestins to enhance lordosis when applied to the ventral tegmental area (VTA), following progesterone to the ventral medial hypothalamus (VMH) was investigated. Ovariectomized, oestrogen-primed rats and hamsters with contralateral VMH/VTA cannulae were tested for lordosis before and after implants of P to the VMH and progestins to the VTA. The progestins were P, 5α-pregnan-3,20-dione (DHP), 5α-pregnan-3α-ol-20-one(3α,5α-THP), 5α-pregnan-3α,21-diol-20-one (THDOC), 5β-pregnan-3α-ol-20-one(3α,5β-THP), 17α-ol-6-methyl-4,6-pregnadiene-3,20-dione-17-acetate (megestrol acetate, MA), and 6-chloro-17-ol-4,6-pregnadiene-3,20-dione-17-acetate (chlormadinone acetate, CA). Progestins’ effects on GABA-mediated chloride influx and SR 95531 binding in cortical and midbrain tissue, respectively, were examined in rats and hamsters. 3α,5α-THP and THDOC implants to the VTA were the most effective at immediately facilitating lordosis of rats and hamsters. Two hours later all other progestins, except MA and CA, increased lordosis in rats; only P, 3α,5α-THP, and THDOC were effective in hamsters. The progestins’ effectiveness at facilitating lordosis were similar to their effects on GABA-stimulated chloride influx and SR 95531 receptor binding (3α,5α-THP and THDOC>P>DHP>3α, 5β-THP>MA and CA). These findings suggest that progesterone lordosis enhancing effects in the rodent VTA may be via GBRs.