Naltrexone Reduces Ethanol‐ and/or Water‐Reinforced Responding in Rhesus Monkeys: Effect Depends Upon Ethanol Concentration

Abstract

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. 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. 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. 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.