Relapse prevention in clean addicts is a great challenge for addiction-therapy. As strong cravings often precede relapse, anti-craving drugs seem to be a promising way for addicts to stay clean. Naloxone and acamprosate are two candidates for anti-craving drugs that are already used for relapse prevention in alcoholic patients. However, it has to be figured out if both drugs are also effective in opiate-addicts. In order to evaluate their effectiveness, a conditioned place preference (CPP) paradigm was used in rats conditioned to 10 mg/kg, i.p., morphine. As acamprosate and naloxone have been suggested to selectively affect different types of craving (withdrawal-craving versus reward-craving), we have tried to modulate craving-behaviour by maintaining two groups of rats under different conditions (isolated versus group-housed). Thereafter, the effectiveness of acamprosate (200 mg/kg, i.p.) and naloxone (2 mg/kg, i.p.) in reducing morphine-CPP expression was evaluated. As a result, isolation produced a weak reduction in morphine-CPP development. Furthermore, acamprosate and naloxone had no effect on morphine-CPP expression. Based on the present results, we assume that the anti-craving drugs acamprosate and naloxone may not be effective for relapse prevention in opiate-addicts. (c) 2004 Elsevier Ireland Ltd. All rights reserved.