Effects of the 5-HT 1A receptor agonist ipsapirone on operant self-administration of ethanol in the rat

Abstract

Although the serotonin (5-HT) 1A receptor agonist ipsapirone reduces ethanol intake in a variety of animal models of alcoholism, such effects have only been reported in models based on nonoperant behavior (e.g., two-bottle choice procedures). It was the aim of the present study to characterize the effects of ipsapirone in an operant model of alcohol self-administration. Rats 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, saccharin-fading procedure. After establishment of stable responding, ipsapirone (0, 2.5–20 mg/kg, intraperitoneal) was tested in combination with different ethanol unit doses (0, 1.25–20%). Ethanol-reinforced responding was related to the ethanol unit dose in an inverted U-shaped manner. Ipsapirone dose-dependently decreased the number of ethanol- and water-reinforced lever responses, irrespective of the ethanol unit dose, and failed to affect ethanol preference. As there was only a minor difference between the minimal effective 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-induced left- or rightward shift of the ethanol unit dose–response curve, the effects 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, nature) with the positive reinforcing stimulus properties of alcohol.