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Background and Ain Druginduced sensitization in the mesocorticolimbic systems has been thought to play an important role in certain aspects of drug addiction, including the important function of drugassociated cues and environments in mediating drugseeking behaviors.Our previous studies have identified a role of heat shock protein 70 (Hsp70) in the development of a single exposure morphineinduced behavioral sensitization.Methods The present study investigated the effect of environment on the expression of behavioral sensitization induced by a single morphine exposure, and associated Hsp70 levels.Results Our results showed that expression of single exposure morphineinduced behavioral sensitization was accompanied by a significant increase of Hsp70 expression in the nucleus accumbens (NAc).In contrast, mice administered morphine in an unpaired fashion failed to exhibit behavioral sensitization or higher Hsp70 expression.Additionally, by using a habituation process before challenge to remove conditioned response, we found that there was a transition from conditioned hyperactivity to behavioral sensitization, the former of which was not accompanied by an increased expression of Hsp70.Conclusions Together, these results suggest that behavioral sensitization induced by a single morphine exposure in mice exhibits contextand timedependent patterns with environmental context functioning probably via an inhibitory conditioning mechanism.Alteration of Hsp70 expression in NAc may represent a neurobiological sensitization mechanism mediating contextand timedependent behavioral sensitization.