Progestins' rapid facilitation of lordosis when applied to the ventral tegmentum corresponds to efficacy at enhancing GABA(A) receptor activity

Progestins may have actions in the midbrain though gamma-aminobutyric acid (GABA)(A)/benzodiazepine receptor complexes (GBRs) that are relevant for se xual receptivity. The efficacy and time course of various progestins to enh ance lordosis when applied to the ventral tegmental area (VTA), following p rogesterone to the ventral medial hypothalamus (VMH) was investigated. Ovar iectomized, oestrogen-primed rats and hamsters with contralateral VMH/VTA c annulae were tested for lordosis before and after implants of P to the VMH and progestins to the VTA. The progestins were P, 5 alpha-pregnan-3,20-dion e (DHP), 5 alpha-pregnan-3 alpha-ol-20-one(3 alpha,5 alpha-THP), 5 alpha-pr egnan-3 alpha,21-diol-20-one (THDOC), 5 beta-pregnan-3 alpha-ol-20-one(3 al pha, 5 beta-THP), 17 alpha-ol-6-methyl-4,6-pregnadiene-3,20-dione-7-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 c hloride influx and SR 95531 binding in cortical and midbrain tissue, respec tively, were examined in rats and hamsters. 3 alpha,5 alpha-THP and THDOC i mplants to the VTA were the most effective at immediately facilitating lord osis of rats and hamsters. Two hours later all other progestins, except MA and CA, increased lordosis in rats; only P, 3 alpha,5 alpha-THP, and THDOC were effective in hamsters, The progestins' effectiveness at facilitating l ordosis were similar to their effects on GABA-stimulated chloride influx an d SR 95531 receptor binding (3 alpha,5 alpha-THP and THDOC > P > DHP > 3 al pha, 5 beta-THP > MA and CA). These findings suggest that progesterone lord osis enhancing effects in the rodent VTA may be via GBRs.