EVIDENCE FOR OVERSHADOWING BY COMPONENTS OF THE HETEROGENEOUS DISCRIMINATIVE STIMULUS EFFECTS OF ETHANOL

The present study used a drug discrimination paradigm to characterize the contribution of separate receptor systems to the stimulus effects of different training doses of ethanol. In a two-lever drug discrimina tion paradigm two groups of adult male Long-Evens rats (n = 8 per grou p) were trained to discriminate either 1.0 g/kg ethanol from water or 2.0 g/kg ethanol from water, administered intragastrically (i.g.), 30 min prior to the start of daily sessions in which responding was maint ained under a fixed ratio 20 schedule of food presentation. Following training, cumulative dosing substitution tests were conducted with the GABA(A) positive modulator pentobarbital (1-17 mg/kg, i.p.), the unco mpetitive NMDA antagonist dizocilpine (0.01-0.3 mg/kg, i.p.) and the 5 -HT1B/2C agonist m-trifluoromethylphenylpiperazine (TFMPP 0.17-1.7 mg/ kg, i.p.). Next, the rats initially trained at 1.0 g/kg ethanol were r etrained to discriminate 2.0 g/kg ethanol from water, and the rats ini tially trained at 1.0 g/kg were retrained to discriminate 2.0 g/kg eth anol from water. Both groups were then re-tested with the same ligands . Regardless of training history, animals currently discriminating 1.0 g/kg were more sensitive to the ethanol-like effects of TFMPP and pen tobarbital compared to rats discriminating 2.0 g/kg ethanol. However, no difference in sensitivity to the ethanol-like effects of dizocilpin e based on ethanol training dose was detected. These results support t he view that ethanol is a heterogeneous discriminative stimulus compri sed of GABA(A), NMDA and 5-HT1B2C receptor-mediated activity. Furtherm ore, changes in sensitivity to GABA(A) and 5-HT ligands as a function of training dose could be indicative of overshadowing by other compone nts of ethanol's heterogeneous cue. Finally, it appears that the curre nt profile of ethanol's heterogeneous stimulus effects, rather than an interaction with ethanol training history, determines the substitutio n pattern of specific receptor ligands. (C) 1998 Elsevier Science Irel and Ltd. All rights reserved.