Effects of gamma-hydroxybutyric acid and flunitrazepam on ethanol intake in male rats

Both gamma-hydroxybutyric acid (GHB) and flunitrazepam are often used illicitly in combination with ethanol. Nevertheless, the effects that these and other drugs of abuse have on the reinforcing effects of ethanol remain inconclusive. To test the effects of GHB and flunitrazepam on contingent ethanol intake, twelve male Long-Evans rats were trained to orally consume ethanol using a saccharin-fading procedure. After training, all animals preferentially consumed ethanol instead of water at each of five ethanol concentrations (0-32%) when tested with a two-bottle preference test in the homecage. Animals then received a noncontingent dose of ethanol (0.32, 0.56, 1, and 1.33 g/kg), flunitrazepam (0.032, 0.1, and 0.32 mg/kg), or GHB (100, 180, 320, and 560 mg/kg) prior to each subject's daily access to ethanol (18% v/v). Noncontingent doses of ethanol decreased ethanol intake, however, the subjects consumed enough ethanol to maintain a consistent total ethanol dose in g/kg. Flunitrazepam did not affect ethanol intake at any dose tested, whereas GHB only affected intake at the highest dose (560 mg/kg), a dose that also produced sedation. These data suggest that there are perceptible or qualitative differences between GHB, flunitrazepam, and ethanol in terms of their capacity for modulating oral ethanol intake in outbred rats.