Progestins may have actions in the midbrain though
gamma-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, 5alpha-pregnan-3,20-dione (DHP), 5alpha-pregnan-3alpha-ol-20-one(3alpha,5alpha-TH P),
5alpha-pregnan-3alpha,21-diol-20-one (
THDOC), 5beta-pregnan-3alpha-ol-20-one(3alpha,5beta-THP) , 17alpha-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. 3alpha,5alpha-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, 3alpha,5alpha-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 (3alpha,5alpha-THP and
THDOC>P>DHP>3alpha, 5beta-THP>MA and CA). These findings suggest that
progesterone lordosis enhancing effects in the rodent VTA may be via
GBRs.