Effects of the 5-HT1A receptor agonist ipsapirone on operant self-administration of ethanol in the rat

Although the serotonin (5-HT)(1A) receptor agonist ipsapirone reduces ethan ol intake in a variety of animal models of alcoholism, such effects have on ly been reported in models based on nonoperant behavior (e.g., two-bottle c hoice procedures). It was the aim of the present study to characterize the effects of ipsapirone in an operant model of alcohol self-administration. R ats were trained during daily 30-min sessions to respond for oral delivery of an ethanol solution (10% w/v) or water in a two-lever, fixed-ratio:1, sa ccharin-fading procedure. After establishment of stable responding, ipsapir one (0, 2.5-20 mg/kg, intraperitoneal) was tested in combination with diffe rent ethanol unit doses (0, 1.25-20%). Ethanol-reinforced responding was re lated to the ethanol unit dose in an inverted U-shaped manner. Ipsapirone d ose-dependently decreased the number of ethanol- and water-reinforced lever responses, irrespective of the ethanol unit dose, and failed to affect eth anol preference. As there was only a minor difference between the minimal e ffective dose which reduced operant responding for ethanol and water (i.e., 10 and 20 mg/kg, respectively), and there was no evidence for a drug-induc ed left- or rightward shift of the ethanol unit dose-response curve, the ef fects of ipsapirone are considered to be nonselective. It is suggested that the ethanol intake-reducing effects of ipsapirone are not the result of a drug-induced interference (either of an attenuating, or potentiating, natur e) with the positive reinforcing stimulus properties of alcohol. (C) 1999 P ublished by Elsevier Science B.V. All rights reserved.