Copulation to satiation induces a series of enduring physiological changes in male rats, with the appearance of a long lasting sexual inhibitory period as the most conspicuous, that are suggestive of the occurrence of neuroplastic changes. Copulation is a natural reward activating the mesocorticolimbic circuit and inducing nucleus accumbens dopamine release. The repeated activation of this system by drug rewards induces neuroplastic changes involving both dopamine and glutamate transmission. We hypothesized that repeated activation of the mesocorticolimbic circuit during copulation to satiation might also activate these neurotransmitter systems. The objective of the present work was to establish the possible participation of glutamate transmission in sexual satiety. To this aim we tested if the systemic injection of specific glutamate receptor antagonists of the NMDA, AMPA and mGluR5 receptor subtypes would reverse the sexual inhibitory state characteristic of sexually satiated rats. Results showed that systemic administration of low doses of the three glutamate receptor antagonists reversed sexual exhaustion evidencing a role for glutamate in the maintenance of the sexual inhibition that follows copulation to satiation, with the participation of NMDA, AMPA and mGluR5 receptors. These glutamate receptor subtypes have been associated to the neuroplastic changes resulting from repeated activation of the mesocorticolimbic circuit by drug rewards, a phenomenon that might also result from its activation by continued copulation.