Background and Aim Drug-induced sensitization in the mesocorticolimbic systems has been thought to play an important role in certain aspects of drug addiction, including the important function of drug-associated cues and environments in mediating drug-seeking behaviors. Our previous studies have identified a role of heat shock protein 70 （Hsp70） in the development of a single exposure morphine-induced behavioral sensitization. Methods The present study investigated the effect of environment on the expression of behavioral sensitization in- duced by a single morphine exposure, and associated Hsp70 levels. Results Our results showed that expression of single exposure morphine-induced behavioral sensitization was accompanied by a significant increase of Hsp70 ex- mice administered morphine in an unpaired fashion failed pression in the nucleus accumbens （NAc）. In contrast, to exhibit behavioral sensitization or higher Hsp70 expression. Additionally, by using a habituation process before we found that there was a transition from conditioned hyperactivity to be- challenge to remove conditioned response, havioral 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 exhib- its context- and time-dependent patterns with environmental context functioning probably via an inhibitory condition- ing mechanism. Alteration of Hsp70 expression in NAc may represent a neurobiological sensitization mechanism mediating context- and time-dependent behavioral sensitization.
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