Increasing cAMP, or activating dopamine type 1 (D(1)) or GABA(A)/benzodiazepine receptor complexes (GBRs), in the ventral tegmental area (VTA) enhances lordosis of rodents. Whether D(1)- and/or GBR-mediated increases in progestin-facilitated lordosis involve the cAMP-synthesizing enzyme, adenylyl cyclase, in the VTA, was investigated. In Experiment 1, ovariectomized estradiol (E(2); 10 microg at h 0)+progesterone (P; 250 microg at h 45)-primed hamsters first received bilateral infusions of the adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine (DDA; 12 microM/side), or vehicle, and then were infused with the D(1) agonist, SKF38393 (100 ng/side), the GBR agonist, muscimol (100 ng/side), or vehicle, to the VTA. Lordosis was evaluated before and 30 min after each infusion. In Experiment 2, ovariectomized, E(2)-primed (10 microg at h 0) rats received VTA infusions of DDA (12 microM/side) or vehicle; SKF38393 (100 ng/side), muscimol (100 ng/side), or vehicle; and the neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP; 100 or 200 ng/side), or beta-cyclodextrin vehicle. Lordosis was assessed before the series of infusions, immediately after drug infusions and 10 or 60 min after 3alpha,5alpha-THP infusions. Progestin- or progestin plus SKF38393-or muscimol-mediated increases in lordosis were blocked by DDA pretreatment. Thus, in the VTA, progestins' membrane action may involve adenylyl cyclase.