In the ventral tegmental area picrotoxin blocks FGIN 1-27-induced increases in sexual behavior of rats and hamsters

Rationale and objectives: There are two types of benzodiazepine receptors, mitochondrial benzodiazepine receptors (MBRs), and γ-aminobutyric acid (GABA)/benzodiazepine receptor complexes (GBRs). MBR activation increases neurosteroidogenesis. Ventral tegmental area (VTA) infusions of the MBR agonist, FGIN 1-27, increase midbrain levels of the progesterone metabolite 5α-pregnan-3α-ol-20-one (3α,5α-THP) and lordosis of rats and hamsters. Activation of GBRs leads to membrane hyperpolarization. In the VTA, infusions of GBR agonists enhance 3α,5α-THP-facilitated lordosis. Thus, if, in the VTA, MBR-mediated increases in 3α,5α-THP enhance sexual responses via actions at GBRs, then blocking GBRs with picrotoxin will reduce FGIN 1-27-induced increases in sexual behavior of female rodents. Methods: Ovariectomized rats and hamsters, with unilateral guide cannula to the VTA, received estradiol benzoate (10 μg; EB) at hour 0. Hamsters also received progesterone (100 μg) at hour 44. At hour 47.5, all animals were infused first with 10 ng or 20 ng picrotoxin or saline, vehicle to the VTA and, 30 min later, with 5 μg/11.4 nM FGIN 1-27 or saline, vehicle. Ten minutes later, animals were tested for sex and motor behavior. Results: Picrotoxin, but not vehicle, infusions blocked FGIN 1-27-mediated increases in lordosis of rats and hamsters, proceptivity of rats, and sexual responsiveness of hamsters. In addition, midbrain 3α,5α-THP levels were higher in animals that received VTA infusions of FGIN 1-27, compared to those infused with saline, vehicle. Conclusion: In the VTA, GBRs are required for MBR-enhanced sexual behavior of EB-primed rats and EB- and progesterone-primed hamsters. © Springer-Verlag 2004.