Study on the role of glycine, strychnine-insensitive receptors (glycineB sites) in the discriminative stimulus effects of ethanol in the rat.

Several recent studies indicate that both competitive and noncompetitive NMDA receptor antagonists substitute for ethanol in a drug discrimination procedure. In the present study we examined compounds from another class of NMDA receptor antagonists--glycine, strychnine-insensitive, receptor (glycineB site) antagonists in rats trained to discriminate between i.p.-administered 1.0 g/kg ethanol (10% v/v) and saline. When the animals met the discriminative criteria, substitution tests were conducted with the noncompetitive NMDA receptor antagonist, memantine (3.0-12.0 mg/kg, i.p.) and selective, glycineB site antagonists--L-701,324 (0.3-3.0 mg/kg, i.p.) and MRZ 2/576 (0.1-10.0 mg/kg, i.p.). Memantine completely substituted for ethanol at the dose of 6.0 mg/kg, which significantly suppressed the rate of responding, L-701,324 substituted for ethanol at the dose of 3.0 mg/kg, which only tended to decrease the response rate. MRZ 2/576 produced maximal ethanol-appropriate responding (50%) at the dose of 5.0 mg/kg, which did not affect the rate of responding. Glycine (200-800 mg/kg, i.p.) did not antagonize the ethanol stimulus. These results indicate that glycine, strychnine-insensitive, site antagonists may induce some ethanol-like stimulus effects in the rat.