The anti-craving drug acamprosate inhibits the conditioned place aversion induced by naloxone-precipitated morphine withdrawal in rats.

The anti-craving drug acamprosate (Ca N-acetylhomotaurinate) is therapeutically used to prevent a relapse in weaned alcoholics. In the present place conditioning study, the effect of this compound on the motivational impact of morphine withdrawal was examined. Withdrawal was precipitated in rats by administration of the opioid antagonist naloxone (0.1 mg/kg, s.c.) 5-6 days after the subcutaneous implantation of a 75 mg morphine pellet. Aversion against the naloxone-paired cues was observed after conditioning in the drug-free state. The acquisition of conditioned place aversion was completely inhibited by the pretreatment with acamprosate (200 mg/kg, i.p.) 12 h and 30 min prior to conditioning. These results clarify that acamprosate inhibits the motivational component of morphine withdrawal and suggest that ethanol and opiates share similar properties in the neuronal mechanisms of conditioned withdrawal and craving.