Progestins' effects on sexual behaviour of female rats and hamsters involving D1 and GABA(A) receptors in the ventral tegmental area may be G-protein-dependent.

Abstract

In the ventral tegmental area (VTA), progestins have actions involving dopamine type 1-like receptors (D(1)) and gamma-aminobutyric acid (GABA)(A)/benzodiazepine receptor complexes (GBRs) for lordosis. Evidence suggests that D(1) and GBRs can have G-protein-mediated effects. We investigated if, in the VTA, inhibiting G-proteins prevents D(1)- and/or GBR-mediated increases in progestin-facilitated lordosis. Hamsters, with bilateral guide cannulae to the VTA, received systemic E(2) (10 microg) at hour 0 and progesterone (P, 250 microg) at hour 45. At hour 48, hamsters were pre-tested for lordosis and infused with the G-protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S, 50 microM/side), or 10% DMSO saline vehicle. Thirty minutes after initial infusions, hamsters were re-tested and then immediately infused with the D(1) agonist, SKF38393 (100 ng/side), the GBR agonist, muscimol (100 ng/side), or saline vehicle. Hamsters were post-tested for lordosis 30 min later. For rats, E(2) (10 microg) priming at hour 0 was followed by lordosis pre-testing at hour 44. After pre-testing, rats received infusions of GDP-beta-S or vehicle, followed by infusions of SKF38393, muscimol, or vehicle and then infusions of the neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP, 100 or 200 ng/side), or beta-cyclodextrin vehicle. Rats were tested immediately after each infusion of SKF38393, muscimol or vehicle, as well as 10 and 60 min after 3alpha,5alpha-THP or vehicle infusions. Inhibiting G-proteins, in the VTA, reduced the ability of systemic P or intra-VTA SKF38393 or muscimol to facilitate lordosis of E(2)-primed hamsters. Blocking G-proteins, in the VTA, prevented SKF38393-, muscimol- and/or 3alpha,5alpha-THP-mediated increases in lordosis of E(2)-primed rats. Thus, progestins' actions in the VTA for lordosis that involve D(1) and/or GBRs may also include recruitment of G-proteins.

• Authors: Cheryl A Frye, Alicia A Walf, Sandra M Petralia
• Journal: Behavioural brain research (Behav Brain Res) Vol. 172 Issue 2 Pg. 286-93 (Sep 25 2006) ISSN: 0166-4328 [Print] Netherlands
• PMID: 16780967 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Dopamine Agents
• GABA Agonists
• Progestins
• Receptors, Dopamine D1
• Receptors, GABA-A
• Thionucleotides
• Guanosine Diphosphate
• Progesterone
• Estradiol
• guanosine 5'-O-(2-thiodiphosphate)
• GTP-Binding Proteins

Topics

• Analysis of Variance
• Animals
• Cricetinae
• Dopamine Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Estradiol (administration & dosage, physiology)
• Female
• GABA Agonists (administration & dosage)
• GTP-Binding Proteins (antagonists & inhibitors, metabolism)
• Guanosine Diphosphate (administration & dosage, analogs & derivatives)
• Microinjections
• Posture (physiology)
• Progesterone (administration & dosage, physiology)
• Progestins (administration & dosage, metabolism)
• Rats
• Rats, Long-Evans
• Receptors, Dopamine D1 (drug effects, metabolism)
• Receptors, GABA-A (drug effects, metabolism)
• Sexual Behavior, Animal (drug effects, physiology)
• Thionucleotides (administration & dosage)
• Ventral Tegmental Area (drug effects, metabolism)