Ethanol-reinforced behaviour in the rat: effects of naltrexone.
It has been repeatedly reported that endogenous opioid pathways play an important role in ethanol drinking behaviour. In line with these findings, a non-selective opioid receptor antagonist, naltrexone, seems to reduce relapse rates in detoxified alcoholics. The aim of the present study was to evaluate the effects of naltrexone on (i) ethanol self-administration; (ii) extinction of responding for ethanol; (iii) reinstatement of ethanol-seeking induced by non-contingent presentations of ethanol-associated stimuli. Male Wistar rats were trained to lever-press for 8% ethanol in an operant procedure where ethanol was introduced in the presence of sucrose. The selectivity of naltrexone's actions was assessed by studying its effects on water-reinforced behaviour in separate control experiments. Acute injections of naltrexone (1 or 3 mg/kg) did not alter ethanol self-administration. Repeated treatment with naltrexone (3 mg/kg, before three consecutive self-administration sessions) progressively reduced ethanol intake. In the extinction procedure, acute administration of 3 mg/kg naltrexone suppressed responding previously reinforced with ethanol. Similarly, naltrexone (1-3 mg/kg) potently and dose-dependently inhibited reinstatement of ethanol-seeking produced by non-contingent deliveries of the liquid dipper filled with 8% ethanol. In the control experiments, lower doses of naltrexone (1-3 mg/kg) did not exert any effect on either reinforced or non-reinforced (extinction) lever-pressing for water. These results indicate that: (i) subchronic treatment with naltrexone leads to progressive reduction of ethanol self-administration; (ii) single doses of naltrexone may increase extinction and attenuate cue-induced reinstatement of ethanol-reinforced behaviour.
Bienkowski
P
P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Kostowski
W
W
Koros
E
E
D000428:Alcohol Drinking / Q000523:psychology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D014867:Water / Q000494:pharmacology
D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D014867:Water; D000431:Ethanol; D009271:Naltrexone