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.
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Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
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