Objective To construct a morphine tolerance model in primarily cultured striatal neurons,and screen the differentially expressed genes in this model using suppression subtractive hybridization (SSH).Methods Sbtracted cDNA libraries were constructed using SSH from normal primarily cultured striatal neurons and long-term morphine treated striatal neurons (10-5 mol/L for 72 hours).To check reliability of the cell culture model,RT-PCR was performed to detect the cAMP-responsive element-binding protein (CREB) mRNA expression.The subtracted clones were prescreened by PCR.The clones containing inserted fragments from forward libraries were sequenced and submitted to GenBank for homology analysis.And the expression levels of genes of interest were confirmed by RT-PCR.Results CREB mRNA expression showed a significant increase in morphine treated striatal neurons (62.8S±1.98) compared with normal striatal neurons (28.43±1.46,P