An NMDA antagonist impairs copulation and the experience-induced enhancement of male sexual behavior in the rat.

Sexual experience facilitates subsequent male sexual behavior; activation of the N-methyl-D-aspartate (NMDA) glutamate receptor may play a role in this experience-induced enhancement. In this article, the authors report that systemic injections of MK-801, an NMDA receptor antagonist, impaired male sexual behavior in sexually naive and sexually experienced male rats. Furthermore, saline-treated rats that received 7 daily exposures to an inaccessible estrous female instead of sexual experience displayed enhancement of copulation on the following day. Injections of MK-801 before each of these exposures inhibited the experience-induced enhancement on the drug-free test on Day 8. These data suggest that stimulation of NMDA receptors enhances sexual performance immediately and mediates the experience-induced enhancement of subsequent copulatory behavior.