title: Mitochondrial benzodiazepine receptors in the ventral tegmental area modulate sexual behaviour of cycling or hormone-primed hamsters.
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 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.
authors.affiliation: Departments of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Frye
authors.forename: S M
authors.initials: SM
authors.lastname: Petralia
mesh_terms: D000818:Animals; D006224:Cricetinae; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D030762:Estrous Cycle; D005260:Female; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007210:Indoleacetic Acids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000648:ultrastructure*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007210:Indoleacetic Acids; D007546:Isoquinolines; D011963:Receptors, GABA-A; C081306:N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; C037850:PK 11195