Naltrexone reduces ethanol- and sucrose-reinforced responding in rhesus monkeys.
These experiments evaluated the ability of naltrexone (NTX) to reduce selectively oral and i.v. ethanol-reinforced responding, and examined the ethanol-NTX interaction in terms of the competitive opioid antagonist property of NTX. Five rhesus monkeys self-administered ethanol or sucrose and concurrently available water. Ethanol concentration was varied from 0.25% to 8% (w/v). Naltrexone (0.032-0.32 mg/kg) or saline was given i.m. 30 min prior to some drinking sessions. NTX (0.32 mg/kg) reduced ethanol-reinforced responding at the concentration that maintained the most responding (1% or 2%). NTX (0.1 mg/kg) reduced ethanol-reinforced responding, both at a low ethanol concentration (0.25%) that produced little ethanol intake (g/kg), and at a higher concentration (4%) with an appreciable intake. Thus, NTX (0.1 mg/kg) shifted the ethanol concentration-consumption curve down, in an insurmountable manner. NTX (0.1 and 0.32 mg/kg) also reduced reinforced responding for sucrose 100 g/l. In another experiment, three rhesus monkeys were given opportunities to self-administer ethanol i.v. NTX (0.1 mg/kg) reduced the number of ethanol injections obtained by the monkeys at all ethanol doses tested (0.01, 0.032, and 0.1 g/kg per injection). The dose-effect curve was also shifted down. These results showed that NTX reduced behavior maintained by either ethanol or sucrose non-selectively. Furthermore, the ability of NTX to suppress ethanol-reinforced responding did not depend on the route of ethanol administration and was not overcome by increasing the concentration or dose per injection of ethanol.
Williams
K L
KL
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
Winger
G
G
Pakarinen
E D
ED
Woods
J H
JH
D000284:Administration, Oral; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013395:Sucrose / Q000494:pharmacology
D000427:Alcohol Deterrents; D000431:Ethanol; D013395:Sucrose; D009271:Naltrexone