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 ethan ol measured in the conditioned place preference (CPP) paradigm in rats. Aft er receiving 15 daily injections of ethanol (0.5 g/kg, i.p.) before the con ditioning trials, rats acquired the preference to the compartment paired wi th 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 sit e of NMDA receptor complex, when co-administered repeatedly with ethanol, p revented the acquisition of ethanol-induced CPP. Dizocilpine alone provoked the development of CPP having some intrinsic rewarding properties. In cont rast, L-701,324 alone did not affect the CPP. These results suggest that th e rewarding properties of ethanol could be, at least in part, due to its ac tion 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 advantag es in terms of safety compared to non-competitive NMDA receptor antagonists .