Ethanol-reinforced behaviour in the rat: effects of uncompetitive NMDA receptor antagonist, memantine

Ethanol has been reported to alter NMDA receptor-mediated biochemical and electrophysiological responses in vitro. The aim of the present study was to evaluate the effects of an uncompetitive NMDA receptor antagonist memantine, in animal models of alcoholism. Male Wistar rats were trained to drink 8% ethanol in a free-choice, limited access procedure. A separate group of animals was trained to lever press for 8% ethanol in an operant procedure where ethanol was introduced in the presence of sucrose. The selectivity of memantine's actions was assessed by studying its effects on food or water consumption in separate control experiments. Memantine (4.5-24 mg/kg) significantly, but not dose dependently, affected ethanol drinking in the limited access procedure. However, only 6 mg/kg memantine selectively decreased ethanol drinking. Memantine did not alter ethanol intake in rats trained to lever press for ethanol in the operant procedure. Only 9 mg/kg memantine reduced operant responding in the extinction procedure in the rats trained to lever press for ethanol. The same dose of memantine significantly reduced the operant behaviour of rats trained to respond for water. These results indicate that: (i) single doses of memantine only moderately and not dose dependently reduce alcohol drinking in the limited access procedure; (ii) memantine produces non-selective effects on operant behaviour in rats trained to lever press for ethanol in an oral self-administration procedure.