Hamsters are highly dependent upon the central actions of
progesterone (P4) for facilitation of sexual behaviour. In the ventral tegmental area (VTA), P4 has actions through its
neurosteroid metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). The effects of enhancing or inhibiting neurosteroidogenesis (and thereby 3alpha,5alpha-THP concentrations), through manipulations of mitochondrial
benzodiazepine receptors, in the VTA on socio-sexual behaviour of female hamsters were examined. Intact, naturally receptive hamsters and ovariectomized (OVX),
hormone-primed hamsters were unilaterally infused via chronic guide
cannula to the VTA with the mitochondrial
benzodiazepine receptor antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboximide (PK-11195) or the mitochondrial
benzodiazepine receptor agonist, N,N-dihexyl-2-(4-fluorophenyl)indole-30-acetamide (FGIN 1-27) and tested for sexual responsiveness and
lordosis.
PK-11195 (5.6, 11.2 or 22.4 nm) to the VTA attenuated sexual responsiveness of naturally receptive or
oestradiol benzoate (EB) + P4-primed hamsters compared to vehicle. In addition,
FGIN 1-27 (11.4 nm) infusions to the VTA increased sexual responsiveness and
lordosis of cycling or OVX, EB + P4-primed hamsters, compared to vehicle infusions. In OVX, EB + P4-primed hamsters, decrements in sexual responsiveness produced by VTA infusions of
PK-11195 (5.6 nm) were attenuated by VTA infusions of 3alpha,5alpha-THP. VTA infusions of
PK-11195 (5.6 nm) or
FGIN 1-27 (11.4 nm), respectively, decreased and increased midbrain levels of 3alpha,5alpha-THP compared to each other. Together, these findings indicate that manipulating actions of mitochondrial
benzodiazepine receptors in the VTA can augment and inhibit neurosteroidogenesis and sexual responsiveness of
hormone-primed and naturally receptive hamsters.