ASSESSMENT OF THE MULTIPLE DISCRIMINATIVE STIMULUS EFFECTS OF ETHANOLUSING AN ETHANOL-PENTOBARBITAL-WATER DISCRIMINATION IN RATS

Previous drug discrimination studies have elucidated the importance of gamma-aminobutyric acid(A) (GABA(A)), N-methyl-D-aspartate (NMDA) glu tamate, and serotonin (5-HT) receptor systems in mediating the discrim inative stimulus effects of ethanol. The present study used a three-ch oice operant drug discrimination procedure in an attempt to determine if salient GABAergic effects could be separated from other stimulus ef fects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n=7) were train ed to discriminate pentobarbital (10.0 mg/kg; intragastrically (i.g.)) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food re inforcement. Stimulus substitution tests were conducted following the administration of allopregnanolone (1.0-17.0 mg/kg; intraperitoncally (i.p.)), diazepam (0.1-7.3 mg/kg; i.p.), midazolam (0.0056-17.0 mg/kg; i.p.), dizocilpine (0.01-0.56 mg/kg; i.p.), phencyclidine (1.0-5.6 mg /kg; i.p.), CGS 12066B (3-30 mg/kg; i.p.), RU 24969 (0.1-5.6 mg/kg; i. p.) and morphine (1 or 3.0 mg/kg; i.p.). Within the group, allopregnan olone and midazolam completely substituted (>80%), and diazepam partly substituted (67%) for the discriminative stimulus effects of pentobar bital. Dizocilpine and phencyclidine partly substituted (58 and 57%, r espectively) for ethanol without substantial pentobarbital-appropriate responding. RU 24969, CGS 12066B and morphine did not result in compl ete substitution for either ethanol or pentobarbital, although RU 2496 9 resulted in partial (68%) pentobarbital substitution. The ability to train the present three-choice discrimination in rats indicates that the discriminative stimulus effects of 10.0 mg/kg pentobarbital mere s eparable from those of 2.0 g/kg ethanol. The results suggest that the pharmacological effects of ethanol, which can control behavior, may se emingly be modified by training conditions (two-versus three-choice di scrimination procedures), to the extent that a receptor system promine ntly linked to the behavioral activity of ethanol (i.e. GABA(A)) appea rs no longer to be involved in the interoceptive effects of the drug.