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 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.
Schreiber
R
R
CNS Research, Bayer-AG, Wuppertal, Germany. rudy.schreiber.rs1@bayer-ag.de
Manze
B
B
Haussels
A
A
De Vry
J
J
D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012054:Reinforcement, Psychology; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014867:Water / Q000008:administration & dosage
D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D014867:Water; D000431:Ethanol; C043077:ipsapirone; D012439:Saccharin