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 similarities between both compounds. Rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg, IP) from saline in a two-lever food-reinforced 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 ethanol (125-1000 mg/kg, IP, ED50 value: 355 mg/kg). In additional cross-generalization tests with ipsapirone (1-30 mg/kg, IP), stimulus substitution for the ethanol cue was not noted (maximal degree of generalization: 33%, at 10 and 30 mg/kg). To confirm the DD findings that ipsapirone does not substitute for ethanol, an alternative cross-familiarization conditioned taste aversion paradigm (CF-CTA) was utilized. In rats, 1000 mg/kg IP ethanol was used as the reference drug producing a conditioned taste aversion (CTA). It was found that preexposure to ethanol (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 abolish ethanol-induced CTA, suggesting again that the ipsapirone stimulus complex is dissimilar to that produced by ethanol. Because the present findings indicate that, in rats, ipsapirone does not substitute for ethanol, it is suggested that the reported ethanol intake-reducing effects of ipsapirone in animal models of alcoholism are not due to simple stimulus substitution.