ETHANOL INTAKE-REDUCING EFFECTS OF IPSAPIRONE IN RATS ARE NOT DUE TO SIMPLE STIMULUS SUBSTITUTION

The present series of experiments was conducted to investigate whether the previously reported ethanol intake reducing effects of the 5-HT1A receptor agonist ipsapirone could be based on possible stimulus simil arities between both compounds. Rats were trained to discriminate etha nol (12.5% w/v, 1000 mg/kg, IP) from saline in a two-lever food-reinfo rced drug discrimination (DD) procedure. Discrimination criterion was reached after a mean number of training sessions of 42. In subsequent generalization sessions, a dose-response curve was established for eth anol (125-1000 mg/kg, IP, ED(50) value: 355 mg/kg). In additional cros s-generalization tests with ipsapirone (1-30 mg/kg, IP), stimulus subs titution for the ethanol cue was not noted (maximal degree of generali zation: 33%, at 10 and 30 mg/kg). To confirm the DD findings that ipsa pirone does not substitute for ethanol, an alternative cross-familiari zation conditioned taste aversion paradigm (CF-CTA) was utilized. In r ats, 1000 mg/kg IP ethanol was used as the reference drug producing a conditioned taste aversion (CTA). It was found that preexposure to eth anol (500-1500 mg/kg, IP) dose-dependently attenuates the CTA produced by this same drug. Full familiarization was noted with 1000 and 1500 mg/kg. In contrast with this, ipsapirone (1-30 mg/kg, IP) failed to ab olish ethanol-induced CTA, suggesting again that the ipsapirone stimul us complex is dissimilar to that produced by ethanol. Because the pres ent findings indicate that, in rats, ipsapirone does not substitute fo r ethanol, it is suggested that the reported ethanol intake-reducing e ffects of ipsapirone in animal models of alcoholism are not due to sim ple stimulus substitution.