Ro 15-4513 selectively attenuates ethanol, but not sucrose, reinforced responding in a concurrent access procedure; comparison to other drugs.
The experiments described in this report used a concurrent access procedure to study ethanol reinforcement. Rats were trained to lever press for a 10% sucrose solution and a 10% ethanol/10% sucrose mixture, and both reinforcers were available on variable-interval 5-s schedules. In baseline and vehicle injection sessions, the animals distributed their responding between both solutions. When injected with the partial inverse benzodiazepine agonist Ro 15-4513 (3, 9, and 18 mg/kg), responding for the ethanol solution decreased while responding for sucrose remained intact. Ethanol injections (0.5 and 1.0 g/kg) engendered a similar profile. Chlordiazepoxide led to an increase in ethanol mix responding at 2 mg/kg and a decrease in ethanol mix responding at higher doses; no dose affected sucrose responding. Morphine (0.5-16 mg/kg) decreased responding for both the ethanol mix and sucrose solutions, more or less simultaneously. Naloxone (0.125-20 mg/kg) selectively reduced ethanol mix responding at low doses, and decreased responding for both reinforcers at high doses. In another group of animals, isocaloric alternatives were concurrently available: 10% ethanol/0.25% saccharin versus 14% sucrose. Injections of Ro 15-4513 and chloridiazepoxide produced similar results as in the first group of rats: an increase in ethanol mix responding with low dose chlordizepoxide, and a decrease in ethanol mix responding with Ro 15-4513. However, naloxone injections did not selectively affect responding for either of the reinforcers when they were isocaloric. These results are discussed in terms of ethanol's neuropharmacological actions.
Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
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D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D013395:Sucrose / Q000494:pharmacology*; D013997:Time Factors
D001386:Azides; D001569:Benzodiazepines; D009270:Naloxone; D000431:Ethanol; D013395:Sucrose; D002707:Chlordiazepoxide; D009020:Morphine; C042957:Ro 15-4513