Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys.
The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1-1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8-4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.
Rodefer
J S
JS
Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA.
Campbell
U C
UC
Cosgrove
K P
KP
Carroll
M E
ME
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018565:Food-Drug Interactions; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D012439:Saccharin / Q000008:administration & dosage / Q000494:pharmacology*; D012646:Self Administration
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D000431:Ethanol; D009271:Naltrexone; D012439:Saccharin; D010622:Phencyclidine