Naltrexone reduces ethanol- and/or water-reinforced responding in rhesus monkeys: Effect depends upon ethanol concentration

Background: The opioid antagonist naltrexone reduces responding for ethanol. If naltrexone produces this effect by blocking ethanol-induced opioid activity, then naltrexone should reduce responding for ethanol regardless of level of the ethanol responding relative to an alternatively available reinforcer. In addition, if naltrexone competitively blocks ethanol-induced opioid activity, then the naltrexone effect may be surmountable by increasing ethanol concentration and, thus, ethanol intake (g/kg). This study was conducted to determine whether naltrexone will selectively reduce ethanol-reinforced responding when the ethanol concentration is varied such that ethanol fluid deliveries are less than, greater than, or equal to the fluid deliveries of concurrently available water. Methods: Four adult male rhesus monkeys were allowed to respond for ethanol or water concurrently for 2 hr per day. Ethanol concentration was either 2%, 8%, or 32%. On various days, either saline or naltrexone (0.1 mg/kg) was given intramuscularly 30 min before the drinking session. Results: When ethanol fluid deliveries were greater than those of water (at 2% ethanol), naltrexone reduced responding for ethanol. When the ethanol and water fluid deliveries were approximately equal (at 8% ethanol), naltrexone reduced both ethanol and water fluid deliveries. When water fluid deliveries were greater than those of ethanol (at 32% ethanol), naltrexone reduced responding for water. Conclusions: Thus, naltrexone reduced responding for the preferred fluid, either ethanol or water, depending on ethanol concentration. The effect was not surmountable by increasing ethanol concentration and, therefore, ethanol intake (g/kg). Naltrexone may reduce ethanol-reinforced responding by a mechanism other than that of blocking ethanol-induced opioid activity. Naltrexone may be inducing an aversive interoceptive state.