Effects of memantine, an NMDA receptor antagonist, on place preference conditioned with drug and nondrug reinforcers in mice.

Antagonists of the N-methyl-D-aspartate (NMDA) receptor complex have been shown to inhibit the expression of place preferences conditioned with several drugs that are abused by humans, which suggests that this class of compounds may be beneficial in the treatment of substance dependence. Therefore it is important to assess the specificity of this effect, of whether inhibitory effects of NMDA receptor antagonists on conditioned drug stimuli generalize to behaviors produced by nondrug reinforcers. The present study was designed to compare the effects of the NMDA receptor channel blocker, memantine, on the expression of place preferences conditioned with: (1) consumption of regular laboratory food; (2) sexual encounters with females; and (3) injection of morphine (10 mg/kg) in adult male Swiss mice. For all three experiments reported here, unconditioned stimuli (food, receptive female or morphine) were presented before the exposures to the "to-be-conditioned" environments. Significant place preferences developed as a result of explicit pairings of the environmental context and food consumption, sexual encounter and morphine administration. Memantine (7.5 mg/kg, given prior to the post-conditioning test) inhibited the expression of place preferences conditioned with morphine and sexual encounter, but had no effects in food-conditioned mice. These findings suggest that the effects of NMDA receptor blockade may not be limited to drug-reinforced behaviors.