Alcohol consumption is enhanced after naltrexone treatment

It is well known that alcohol increases opioid activity, which can contribute to the reinforcing effect of alcohol. Clinical studies have supported reductions in alcohol consumption among alcoholic patients during treatment with opioid antagonists (OAs) and its use is recommended for this purpose. Experimental studies have demonstrated opioid receptor up-regulation after several days of OA treatment, which increases the availability of these receptors. On this basis, the physiological conditions in the period immediately after the OA treatment could increase the reinforcing value of alcohol and in this way enhance alcohol consumption.

To test this hypothesis, 2 groups of Wistar male rats were used in the present study. After assessing the baseline of voluntary alcohol (10% v/v) consumption, subjects were treated with either the OA naltrexone (Ntx), (2 mg/kg/d/rat) or a saline solution (0.2 mL/d/male) for 7 days. Subsequently, all subjects were given a free choice between ethanol (10%) and water for 5 days. To study a possible cumulative effect, this procedure was sequentially repeated 4 times with each group. Water and food were available ad libitum throughout the experiment.

After each period of 7 days of Ntx use, alcohol consumption increased significantly with respect to the baseline and each equivalent period in the control group. When the subjects were exposed to alcohol again 1 week after the last of the 4 sequential periods, alcohol drinking was higher than the baseline in the Ntx group, but not in the control group. Water consumption was decreased during Ntx treatment in the control group in periods 1, 2, and 4. Food intake and body weight did not show differences between groups throughout the study; however, a decrease in food intake was observed over time regardless of treatment.

These results show that alcohol intake may increase after the Ntx treatment, particularly when alcohol is not available during treatment with the OA, and that this may be due to a higher availability of opioid receptors in that period.