Rationale: Progesterone (P4) has actions in the ventral tegmental area (VTA) to regulate female sexual behavior in rodents. However, there are few intracellular progestin receptors (PRs) that have been identified in the VTA through which P4 may have its actions to facilitate lordosis. There are N-methyl-D: -aspartate receptors (NMDARs) in the VTA that may be a substrate for P4's effects.
Objective: We investigated the effects of pharmacologically manipulating NMDARs in the VTA for E2- and P4-facilitated lordosis of hamsters and rats.
Materials and methods: We examined the effect of systemic injections (intraperitoneal; IP) and bilateral infusions to the VTA of the highly specific, competitive NMDAR antagonist, 9-0-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959); 0, 0.3, and 1 mg/kg IP and 0, 1.0, and 10 ng/mul intra-VTA), on lordosis of estradiol-primed (E2; 10 microg) and P4-primed (0, 50, 250, or 500 microg) ovariectomized hamsters and rats.
Results: Intra-VTA administration of the NMDAR antagonist, LY235959, produced similar effects as systemic administration to enhance lordosis, particularly in E2-primed rats or hamsters administered moderate P4 levels (less than 500 microg). Administration of LY235959 to the substantia nigra did not produce similar effects as intra-VTA infusions for lordosis.
Conclusions: Together, these data suggest that blocking NMDARs in the VTA enhances lordosis of hamsters and rats.