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

Abstract

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.