Conditioned effects produced by naltrexone doses that reduce ethanol-reinforced responding in rhesus monkeys

Clinical trials have shown that naltrexone is effective in treating alcohol dependence; nausea and dysphoria have been reported as "side effects" in m any of these studies. In primates, naltrexone reduces reinforced responding for oral ethanol, sucrose, and phencyclidine. This study was designed to d etermine if naltrexone reduces reinforced responding for various solutions by producing an interoceptive stimulus that may result in a conditioned tas te aversion. Four opioid antagonist-naive rhesus monkeys responded for solu tions from a two-spout operant panel for 30 min per day. During a condition ing phase, the monkeys received novel Kool-Aid(R) solutions paired with eit her saline or naltrexone (0.32 mg/kg) given 30 min before the session. The monkeys then had seven choice sessions between the saline-paired solution o r the naltrexone-paired solution. During the conditioning phase, the naltre xone reduced responding after five naltrexone/solution pairings. In additio n, a conditioned taste aversion was produced; the naltrexone-paired solutio n maintained significantly less responding than did the saline-paired solut ion during the choice phase. In the next phase, the saline and naltrexone w ere given "unpaired" from any distinct part of the operant session, and ano ther seven choice sessions followed. Naltrexone had no effect when given "u npaired" from the operant session. Then, another conditioning phase was und ertaken followed by another series of choice sessions. During the replicati on of the conditioning, naltrexone reduced responding by the second pairing , although no conditioned aversion was observed in the subsequent choice se ssions. Thus, given in the same manner (dose, route, and pretreatment time) as situations in which naltrexone reduces oral ethanol-, sucrose-, and phe ncyclidine-reinforced responding, naltrexone produced a conditioned taste a version. These results suggest that naltrexone-induced nausea and its condi tioned effects should be considered in naltrexone's effect in alcoholics.