Ethanol-reinforced behaviour in the rat: effects of naltrexone

• Published in: European journal of pharmacology 1999-06, Vol.374 (3), p.321-327
• Main Authors: Bienkowski, Przemyslaw, Kostowski, Wojciech, Koros, Eliza
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - psychology; Alcoholism and acute alcohol poisoning; Analysis of Variance; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Central Nervous System Depressants - pharmacology; Conditioning, Operant - physiology; Ethanol - pharmacology; Ethanol self-administration; Extinction; Extinction, Psychological - drug effects; Male; Medical sciences; Naltrexone; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Opioid receptor; Rat; Rats; Rats, Wistar; Reinforcement (Psychology); Reinstatement; Relapse; Self Administration; Toxicology; Water - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00245-9

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.