GABA(A), D1, and D5, but not progestin receptor, antagonist and anti-sense oligonucleotide infusions to the ventral tegmental area of cycling rats and hamsters attenuate lordosis.

Abstract

In hamsters, progesterone (P) in the hypothalamus and ventral tegmental area (VTA) is necessary for receptivity; in rats, hypothalamic P induces receptivity and midbrain P further enhances it. How P exerts its effects in the VTA on lordosis is of interest because few estrogen-induced P receptors (PRs) have been identified there. Sexual receptivity of rats and hamsters is enhanced when P's actions in the VTA are restricted to the membrane and when the gamma-aminobutyric acid (GABA)A agonist, muscimol, is infused into the VTA, but attenuated with infusions of the GABA(A) antagonist, bicuculline. The dopamine (DA) agonist. SKF38393, rapidly enhances receptivity when infused intravenously; this effect can be blocked by both DA receptor (DR) and PR antagonists. This study investigated the importance of PRs, glutamic acid decarboxylase (GAD), the enzyme responsible for GABA production, GABA(A) receptors (GBRs), and DRs in the VTA of cycling rats and hamsters for the expression of lordosis. Proestrous and diestrous animals implanted with bilateral VTA cannulae were pre-tested for receptivity, infused with either an antagonist (RU38486 (20 microg), bicuculline (100 ng), SCH23390 (100 ng)), anti-sense oligonucleotide (against PR (250 ng), GAD (500 ng), D1 (500 ng), D5 (250 ng)), or control infusions to each cannulae and re-tested. Vehicle and scrambled oligonucleotides were infused as controls and elicited similar effects. Antagonists of GBRs and DRs significantly reduced lordosis on post-tests compared to the PR antagonist and control conditions in rats and hamsters. Lordosis was significantly reduced, compared to controls, only by anti-sense oligonucleotides for GAD and D1- and D5-DR subtypes. These data suggest that in the VTA GABAergic and dopaminergic neurons may be more important in the mediation of sexual receptivity than neurons containing intracellular PRs.

• Authors: C A Frye, J M Vongher
• Journal: Behavioural brain research (Behav Brain Res) Vol. 103 Issue 1 Pg. 23-34 (Aug 1999) ISSN: 0166-4328 [Print] Netherlands
• PMID: 10475161 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Benzazepines
• Dopamine Antagonists
• Drd5 protein, rat
• GABA Antagonists
• Oligonucleotides, Antisense
• Progestins
• Receptors, Dopamine D1
• Receptors, GABA-A
• Receptors, Dopamine D5
• Mifepristone
• Bicuculline

Topics

• Animals
• Benzazepines (pharmacology)
• Bicuculline (pharmacology)
• Cricetinae
• Dopamine Antagonists (pharmacology)
• Estrus (drug effects, physiology)
• Female
• GABA Antagonists (pharmacology)
• Mifepristone (pharmacology)
• Oligonucleotides, Antisense (administration & dosage, pharmacology)
• Posture
• Progestins (metabolism)
• Rats
• Rats, Long-Evans
• Receptors, Dopamine D1 (drug effects)
• Receptors, Dopamine D5
• Receptors, GABA-A (physiology)
• Sexual Behavior, Animal (drug effects)
• Ventral Tegmental Area (anatomy & histology, physiology)