Effects of naltrexone administered repeatedly across 30 or 60 days on ethanol consumption using a limited access procedure in the rat.

The present study examined the effects of naltrexone, 1.0 mg/kg, administered repeatedly across both 30 and 60 days on the consumption of an unsweetened ethanol solution by outbred Wistar rats in a limited access procedure. Naltrexone significantly suppressed consumption of ethanol across both 30 and 60 days. These results provide no evidence for the development of tolerance based on such factors as receptor upregulation or supersensitivity due to the repeated administration of naltrexone across extended periods. Ethanol consumption during the final one-third of the naltrexone sessions, for both the 30- and 60-day groups, was significantly lower than during the initial sessions. These results suggest an associative component. That is, the rats apparently learned that ethanol consumption was no longer reinforcing across repeated exposures. After termination of naltrexone treatment, consumption of ethanol immediately increased. However, consumption in those rats who were administered naltrexone for 60 days remained significantly suppressed, compared with consumption in those rats who were administered naltrexone for 30 days. These results suggest that naltrexone reduces ethanol consumption by blocking endogenous opioid receptors that mediate, at least in part, ethanol's reinforcing properties. In addition, these data suggest that longer clinical use of naltrexone, as a pharmacological adjunct to psychosocial treatment for alcohol-dependent patients, may be beneficial in reducing the number of relapses experienced.