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OBJECTIVE AND METHODS To investigate the potential role of PDE10A in the reinforcement of morphine, we observed the effect of MP-10, a selective inhibitor of PDE10A, on the acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP).RESULTS The results show that 2.5 mg· kg-1 MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP.Same dose of inhibitor, administered alone, did not result in the acquisition of CPP.Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP.Additionally, we detected a decreased expression of phosphorylated cAMP response element binding protein (pCREB) in dorsomedial striatum, shell of NAc, and anterior cingulated cortex (ACC), and decreased expression of AFosB in shell of NAc and ACC in response to chronic MP-10 (2.5 mg·kg-1 sc) treatment.CONCLUSION These results imply that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.