Blockade of the acquisition of ethanol-induced conditioned place preference by N-methyl-D-aspartate receptor antagonists

We have examined the influence of two different N-methyl-D-aspartate (NMDA) receptor antagonists on acquisition of the reinforcing properties of ethanol measured in the conditioned place preference (CPP) paradigm in rats. After receiving 15 daily injections of ethanol (0.5 g/kg, i.p.) before the conditioning trials, rats acquired the preference to the compartment paired with ethanol injections during conditioning. Both dizocilpine (0.1 mg/kg, i.p.), a non-competitive antagonist of the NMDA receptor, and L-701,324 (5 mg/kg, per os), an antagonist acting at the strychnine-insensitive glycine site of NMDA receptor complex, when co-administered repeatedly with ethanol, prevented the acquisition of ethanol-induced CPP. Dizocilpine alone provoked the development of CPP having some intrinsic rewarding properties. In contrast, L-701,324 alone did not affect the CPP. These results suggest that the rewarding properties of ethanol could be, at least in part, due to its action at the NMDA receptor complex. Additionally, we can speculate that NMDA receptor antagonists can be useful in the treatment of ethanol dependence. Glycine receptor antagonists having no abuse potential might have advantages in terms of safety compared to non-competitive NMDA receptor antagonists.