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.
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: S K Mani; A A Fienberg; J P O'Callaghan; G L Snyder; P B Allen; P K Dash; A N Moore; A J Mitchell; J Bibb; P Greengard; B W O'Malley Journal: Science Date: 2000-02-11 Impact factor: 47.728