The effects of prior exposure to a high, repeated dose regimen of MDMA on the rewarding properties of other drugs as measured through conditioned place preference (CPP), an indirect measure of rewarding drug effects, was investigated in rats. (Conditioned place preference refers to increased time spent in an area previously paired with a specific drug). Lister Hooded rats were first given vehicle or three 10 mg/kg doses MDMA every 2 h for 6 h. Comparisons were then made on degree of conditioned place preference to 3 mg/kg d-amphetamine, 20 mg/kg cocaine, 2 g/kg ethanol, 0.5 mg/kg heroin or 10 mg/kg MDMA. (Optimal drug doses for producing conditioned place preference were first established via pilot studies). Dose response studies found that only the highest doses of heroin and MDMA produced conditioned place preference in rats. MDMA pre-treatment did not change the degree of conditioned place preference seen for d-amphetamine, cocaine, heroin, or MDMA. However, MDMA pre-treatment eliminated conditioned place preference after ethanol. The authors conclude that a repeated, high-dose regimen of MDMA attenuates the rewarding properties of ethanol. These findings are somewhat surprising given that previous studies found that MDMA pretreatment increased the reward value of cocaine in rats (Fone et al. 2002; Fletcher et al. 2001). The authors did not perform histological analyses of brain serotonin content after MDMA pretreatment, so changes in CPP after ethanol may not necessarily be due to MDMA neurotoxicity. However, other studies have indicated that behavioral changes can occur even after non-neurotoxic doses of MDMA (Fone et al. 2002). If repeated and heavy use of ecstasy produces similar results in humans, it is possible that some ecstasy users may drink ethanol (e.g. alcohol) more heavily in order to produce previously rewarding effects. On the other hand, some ecstasy users may reduce ethanol intake after finding that it is no longer rewarding.