Mitochondrial Benzodiazepine Receptors in the Ventral Tegmental Area Modulate Sexual Behaviour of Cycling or Hormone-Primed Hamsters


    loading  Checking for direct PDF access through Ovid

Abstract

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 5α-pregnan-3α-ol-20-one (3α,5α-THP). The effects of enhancing or inhibiting neurosteroidogenesis (and thereby 3α,5α-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 3α,5α-THP. VTA infusions of PK-11195 (5.6 nM) or FGIN 1-27 (11.4 nM), respectively, decreased and increased midbrain levels of 3α,5α-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.

    loading  Loading Related Articles