The NMDA receptor antagonist MK-801 produces ethanol-like discrimination in the rat

Two groups of rats, one derived from N/Nih stock and the second from the (putatively) serotonin-compromised Fawn-Hooded line, were trained to discriminate ethanol from its vehicle in a drug discrimination paradigm. Once each of the two groups attained discrimination criterion, dose-response relationships with lower doses of ethanol indicated that the Fawn-Hooded rats were less sensitive (ED 50 value = 579.5 mg/kg) than the N/Nih rats (ED 50 = 371.4 mg/kg). Testing of various doses of the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 produced complete generalization in each group of animals, with a similar difference in ED 50 values between N/Nih and Fawn-Hooded lines. These results extend previous ethanol-to-MK-801 generalization reported in pigeons, and are discussed in light of a possible NMDA-mediated contribution to the ethanol-induced discriminative stimulus cues.