Discrimination of gamma-hydroxybutyrate and ethanol administered separately and as a mixture in rats

The physiological effects of gamma-hydroxybutyrate (GHB) are complex and no t yet clearly defined. GHB has been labeled as a recreational drug and is r eported to be frequently coabused with ethanol (ETH). Other studies have yi elded discrepant results as to the interaction between GHB and ETH. Thus, t he present study investigated extensively the discriminative stimulus of GH B and ETH and a mixture of the two compounds. Thirty male Long-Evans rats w ere divided into three groups and trained to discriminate doses of either 3 00 mg/kg GHB, 1000 mg/kg ETH, or a mixture (MIX: 150 mg/kg GHB + 500 mg/kg ETH) from vehicle on a two-lever fixed-ratio (FR) 10 schedule of food reinf orcement. Dose-response curves were attained in each group with its respect ive training drugs. GHB and ETH did not cross-generalize in the ETH- and GH B-trained rats, respectively. However, when the effects of the MIX were tes ted in the GHB- and ETH-trained rats, a greater than additive response was observed. Testing also revealed that the MIX-trained rats did not perceive a novel stimulus but a near-equal contribution from GHB and ETH. This study provides evidence of a complex relationship between GHB and ETH and oppose s previous work reporting cross-generalization between GHB and ETH. (C) 200 1 Elsevier Science Inc. All rights reserved.