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

The physiological effects of gamma-hydroxybutyrate (GHB) are complex and not yet clearly defined. GHB has been labeled as a recreational drug and is reported to be frequently coabused with ethanol (ETH). Other studies have yielded discrepant results as to the interaction between GHB and ETH. Thus, the present study investigated extensively the discriminative stimulus of GHB and ETH and a mixture of the two compounds. Thirty male Long-Evans rats were divided into three groups and trained to discriminate doses of either 300 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 reinforcement. Dose-response curves were attained in each group with its respective training drugs. GHB and ETH did not cross-generalize in the ETH- and GHB-trained rats, respectively. However, when the effects of the MIX were tested 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 opposes previous work reporting cross-generalization between GHB and ETH.