Increased specificity of ethanol's discriminative stimulus effects in an ethanol-pentobarbital-water discrimination in rats

Abstract

Ethanol's modulation of a number of receptor systems results in a heterogeneous discriminative stimulus complex. A previous study found that these heterogeneous discriminative stimulus effects were seemingly diminished when rats were trained to discriminate ethanol (2.0 g/kg) from pentobarbital (10.0 mg/kg). The present experiment was designed to extend these findings by using a lower training dose of ethanol (1.0 g/kg). Adult male Long-Evans rats (n = 7) discriminated pentobarbital (10.0 mg/kg; intragastric (i.g.)) from ethanol (1.0 g/kg; i.g.) from water (2.3 ml; i.g.) in a 3 lever, food-reinforced task. Substitution tests were conducted following intraperitoneal (i.p.) administration of GABA(A) positive modulators, noncompetitive NMDA antagonists, 5-HT1 agonists and isopropanol. The GABA(A) positive modulators diazepam, midazolam and allopregnanolone completely substituted for pentobarbital. Isopropanol completely substituted for ethanol, while the NMDA antagonists dizocilpine and phencyclidine partially substituted for ethanol. The 5-HT agonists RU 24969 and CGS 12066B did not result in complete substitution for ethanol or pentobarbital, although RU 24969 resulted in partial pentobarbital substitution. These data replicate and extend the previous findings that discriminating ethanol from pentobarbital attenuates the ethanol-like effects of GABA(A) positive modulators, NMDA antagonists and 5-HT1 agonists and results in a more specific ethanol cue. The outcome appears to be a conditional basis for the ethanol discrimination, where a full ethanol-like effect is produced only by drugs with pharmacological activity similar to the heterogenous effects of ethanol (e.g. other alcohols).