In the ventral tegmental area, G-proteins mediate progesterone's actions at dopamine type 1 receptors for lordosis of rats and hamsters.

Abstract

RATIONALE:

Previous reports indicate that the ventral tegmental area (VTA) and/or progesterone (P) can modulate the reinforcing effects of drugs of abuse, food, and sexual behavior.

OBJECTIVES:

We investigated if, in the VTA, P's membrane-mediated actions for lordosis involve dopamine type 1 receptors (D(1)). Also, whether P's actions at D(1) for lordosis are mediated by typical G-protein coupled mechanisms was examined.

METHODS:

In Exps 1 and 2, rats received estradiol (E(2) 10 microg) at h 0 and infusions of the D(1) antagonist SCH23390 (100 ng), the D(1) agonist SKF38393 (100 ng), or vehicle, to the VTA, at h 44. Thirty minutes later, rats received systemic P (0, 50, 100, or 200 microg). Subjects were tested for lordosis and motor behavior 2.5 h later. In Exps 3 and 4, E(2)+P (rats 0 or 100 microg; hamsters 200 microg)-primed animals were pretested for lordosis and motor behavior at h 47.5 and infused with SKF38393 (100 ng) or vehicle to the VTA. Thirty minutes later, subjects were retested and infused with the G-protein inhibitor guanosine 5'-O-(2-Thiodiphosphate) (GDP-beta-S; 50 microM) or vehicle. Post-testing occurred 30 min later.

RESULTS:

Pretreatment with SCH23390-reduced and SKF38393-enhanced P's actions, in the VTA, for lordosis of E(2)-primed rats and hamsters. As well, D(1)-mediated increases in P-facilitated lordosis of rats and hamsters were inhibited by GDP-beta-S. Changes in lordosis were independent of large alterations in motor behavior.

CONCLUSIONS:

In the VTA, P has actions for modulating reinforcing behaviors, such as lordosis, at D(1) that are G-protein-mediated.

• Authors: Sandra M Petralia, Cheryl A Frye
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 186 Issue 2 Pg. 133-42 (Jun 2006) ISSN: 0033-3158 [Print] Germany
• PMID: 16482481 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Benzazepines
• Dopamine Agonists
• Dopamine Antagonists
• Receptors, Dopamine D1
• Progesterone
• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• GTP-Binding Proteins

Topics

• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (pharmacology)
• Animals
• Behavior, Animal (drug effects, physiology)
• Benzazepines (pharmacology)
• Cricetinae
• Dopamine Agonists (pharmacology)
• Dopamine Antagonists (pharmacology)
• Female
• GTP-Binding Proteins (metabolism)
• Lordosis (metabolism, physiopathology)
• Motor Activity (drug effects, physiology)
• Ovariectomy
• Progesterone (pharmacology)
• Rats
• Rats, Long-Evans
• Receptors, Dopamine D1 (agonists, antagonists & inhibitors, metabolism)
• Ventral Tegmental Area (drug effects, metabolism)