An NMDA receptor antagonist reduces ethanol preference in untrained but not trained rats

Rats were exposed to a potent antagonist of NMDA receptors, 2-amino-5 phosphonovalerate (AP5) by implanting osmotic pumps delivering AP5 (test group) or the vehicle for AP5 (control group) into the cerebrospinal fluid through previously implanted cannulas. A week later they were given the choice of 6% ethanol or water for 1 h. The control group had a significantly greater preference for ethanol than the test group after the first 5 days. Another group of rats was trained almost to a 100% criterion in preferring ethanol to water in the hour the choice was available. Then they were implanted with osmotic pumps and cannulas and administered AP5. These trained rats showed no significant difference between control and test groups in preference for ethanol after the first 5 days. The results support the hypothesis that activation of NMDA receptors is involved in learning to drink ethanol.