Development of Naltrexone Supersensitivity During Food‐Maintained Responding Enhances Naltrexone's Ability to Reduce Ethanol‐Maintained Responding

Abstract

Similar doses of the opiate antagonist naltrexone (NTX) reduce responding maintained by food and ethanol. In animals responding for food, repeated administration of NTX produces supersensitivity to NTX. The purpose of this study was to determine whether the factors that produce enhanced sensitivity to NTX during food-maintained responding also contribute to NTX's ability to reduce ethanol-maintained responding. Rats (n=12) were trained to lever press using food reinforcement. After responding stabilized, the rats were trained to respond for 10% ethanol. Before ethanol sessions, injections of 30 mg/kg NTX were given. Subsequently, weekly cumulative NTX dose-effect curves (1, 3, 10, 30, and 100 mg/kg), known to produce NTX supersensitivity, were determined during food-maintained responding in half the rats for 8 weeks while the other half of the rats received saline vehicle injections instead. To determine whether NTX supersensitivity would transfer to ethanol self-administration, ethanol-maintained responding was re-established and 30 mg/kg NTX was administered again. Initially, 30 mg/kg NTX had little effect on ethanol-maintained responding. During food-maintained responding, supersensitivity developed in rats receiving weekly cumulative NTX injections. After development of supersensitivity, 30 mg/kg decreased ethanol-maintained responding. Naltrexone's potency to reduce ethanol-maintained responding was unchanged in rats that received only vehicle injections for 8 weeks. The mechanisms that produce NTX supersensitivity during food-maintained responding may play a role in NTX's effect on ethanol consumption. Naltrexone's effect on responding for ethanol was much smaller than that reported in other studies. Further exploration may lead to techniques that maximize NTX's effect on ethanol while minimizing its effect on other behaviors.