The response to naltrexone in ethanol-drinking rats depends on early environmental experiences

Abstract

The opioid receptor antagonist naltrexone is currently used in the treatment of alcohol addiction. However, substantial individual differences have been reported for the efficacy of naltrexone. Genetic factors are known to contribute to these differences; however, little is known about the impact of early environmental influences. Based on previous findings that have suggested a link between ethanol, endogenous opioids and the early environment, it was hypothesised that early environmental factors affect naltrexone efficacy later in life. A population of Wistar rats was subjected to three different rearing conditions where the pups experienced a daily separation from the dam, for either 15min or 360min, or were just briefly handled. On postnatal day 26, the rats were given intermittent access to ethanol (5% and 20%) and water for six weeks before naltrexone (0.3mg/kg or 3.0mg/kg) or saline treatment using a randomised injection schedule with a one-week washout period between injections. Naltrexone reduced ethanol consumption, but there was high variability in the efficacy. In addition, there was an association between the rearing condition and the effectiveness of naltrexone. Naltrexone reduced ethanol intake in rats experiencing postnatal conditions that contrasted normal wildlife conditions, i.e., prolonged absence or continuous presence of the dam, and naltrexone had no effect on the total ethanol consumption in rats reared under naturalistic conditions, i.e., short absences of the dam. These rats reduced their intake of 5% ethanol but increased their preference for 20% ethanol. We conclude that rats with a history of early adversity responded well to naltrexone treatment, whereas rats reared in a social context similar to that found in nature did not benefit from treatment. The present study highlights the importance of not only considering genetics but also environmental factors when identifying individual responses to naltrexone.