Journal of Neuroendocrinology 2003-07-01

Mitochondrial benzodiazepine receptors in the ventral tegmental area modulate sexual behaviour of cycling or hormone-primed hamsters.

C A Frye, S M Petralia

文献索引：J. Neuroendocrinol. 15(7) , 677-86, (2003)

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摘要

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.