Progestins' effects on sexual behaviour of female rats and hamsters involving D1 and GABA(A) receptors in the ventral tegmental area may be G-protein-dependent.

In the ventral tegmental area (VTA), progestins have actions involving dopamine type 1-like receptors (D(1)) and gamma-aminobutyric acid (GABA)(A)/benzodiazepine receptor complexes (GBRs) for lordosis. Evidence suggests that D(1) and GBRs can have G-protein-mediated effects. We investigated if, in the VTA, inhibiting G-proteins prevents D(1)- and/or GBR-mediated increases in progestin-facilitated lordosis. Hamsters, with bilateral guide cannulae to the VTA, received systemic E(2) (10 microg) at hour 0 and progesterone (P, 250 microg) at hour 45. At hour 48, hamsters were pre-tested for lordosis and infused with the G-protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S, 50 microM/side), or 10% DMSO saline vehicle. Thirty minutes after initial infusions, hamsters were re-tested and then immediately infused with the D(1) agonist, SKF38393 (100 ng/side), the GBR agonist, muscimol (100 ng/side), or saline vehicle. Hamsters were post-tested for lordosis 30 min later. For rats, E(2) (10 microg) priming at hour 0 was followed by lordosis pre-testing at hour 44. After pre-testing, rats received infusions of GDP-beta-S or vehicle, followed by infusions of SKF38393, muscimol, or vehicle and then infusions of the neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP, 100 or 200 ng/side), or beta-cyclodextrin vehicle. Rats were tested immediately after each infusion of SKF38393, muscimol or vehicle, as well as 10 and 60 min after 3alpha,5alpha-THP or vehicle infusions. Inhibiting G-proteins, in the VTA, reduced the ability of systemic P or intra-VTA SKF38393 or muscimol to facilitate lordosis of E(2)-primed hamsters. Blocking G-proteins, in the VTA, prevented SKF38393-, muscimol- and/or 3alpha,5alpha-THP-mediated increases in lordosis of E(2)-primed rats. Thus, progestins' actions in the VTA for lordosis that involve D(1) and/or GBRs may also include recruitment of G-proteins.