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.
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
K L
KL
Williams
G
G
Winger
E D
ED
Pakarinen
J H
JH
Woods
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