DOPAMINERGIC REGULATION OF PROGESTERONE RECEPTORS - BRAIN D5 DOPAMINE-RECEPTORS MEDIATE INDUCTION OF LORDOSIS BY D1-LIKE AGONISTS IN RATS

To characterize the signaling pathway by which the neurotransmitter do pamine modulates progesterone receptor (PR) activation, the steroid-de pendent behavior lordosis was used in estrogen-primed ovariectomized S prague-Dawley rats with stereotaxic implanted third ventricle cannulas . Lordosis was observed in response to solicitous males in females aft er central administration of the D1-like agonist SKF38393 and three of its analogs (SKF77434, SKF75640, and SKF85174). In contrast, D1-like antagonist SCH23390 and D1-like/D2 repopulation inhibitor EEDQ blocked behavior inducible by the D1-like agonists. Further, antisense oligon ucleotides to D5, but not D1, dopamine receptor mRNA suppressed reprod uctive behavior associated with D1-like stimulation. This finding prov ides strong evidence that dopaminergic modulation of lordosis is media ted by the novel D5 dopamine receptor. Although D1, but nor D5, dopami ne receptor mRNAs were detected in the ventromedial nucleus (VMN) by i n situ hybridization, agonists microinjected into the VMN, but not int o the arcuate nucleus or preoptic area, induced lordosis, suggesting t he functional presence of D5 dopamine receptors in the VMN. Also in su pport, D5 receptor mRNA antisense microinjected into the VMN blocked t he subsequent induction of lordosis by D1-like agonists. finally, faci litation of sex behavior by D1-like agonists was blocked by the antipr ogestin RU38486 and PR antisense oligonucleotide. Collectively, the da ta provide strong evidence for dopaminergic modulation of reproductive behavior through D5 dopamine receptor-mediated modulation of PR-depen dent behavior in rat CNS.