In the ventral tegmental area (VTA), progesterone's membrane-mediated actions to facilitate lordosis may involve activation of dopamine type 1 (D1) receptors. Given that D1 receptor activation induces increases in G-protein recruitment, adenosine 3',5' monophosphate (CAMP), the cAMP-dependent protein kinase, protein kinase A (PKA) and phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kD (DARPP-32), experiments examined whether this intracellular signaling cascade is involved in D1 receptor-mediated increases in progesterone-facilitated lordosis of rodents. Ovariectomized rats or hamsters with bilateral guide cannulae to the VTA were 17β-estradiol-primed and then administered systemic progesterone or intra-VTA infusions of progesterone's metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), so that combined effects of activating D1 preceptors, with SKF38393 (100 ng), and inhibiting G-proteins, adenylyl cyclase, PKA or DARPP-32 could be examined. VTA infusions of the G-protein inhibitor, GDP-β-S (50 μM), reduced the enhancing effects of SKF38393 on progesterone-facilitated lordosis of rats and hamsters. SKF38393-meddated increases in progesterone-facilitated lordosis of rats and hamsters were reduced by subsequent infusions of the adenylyl cyclase inhibitor, dideoxyadenosine (12 μM). The inhibiting effects of the D1 antagonist, SCH23390 (100 ng), on progestin-facilitated lordosis of rats were reversed by subsequent infusions of the cAMP agonist 8-bromo-CAMP. Pretreatment with the PKA inhibitor, Rp-cAMP (100 ng), blocked progestin- or progestin plus SKF38393-mediated increases in lordosis of rats and hamsters. Knocking down DARPP-32 in the VTA with infusions of anti-sense oligonucleotides prevented progesterone- or progesterone plus SKF38393-induced increases in lordosis of rats and hamsters. As a whole, these findings suggest that progestins' actions for lordosis are conserved across rodent species and involve activation of D1 receptors, recruitment of G-proteins, increases in cAMP and PKA, and phosphorylation of DARPP-32.