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The reinforcing and psychomotor effects of morphine involve opiate stimulation of the dopaminergic system via activation of μ-opioid receptors (μOR). Both μ-opioid and dopamine receptors are members of the G-protein-coupled receptor (GPCR) family of proteins. GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of βarrestins, which prevents further receptor-G-protein coupling. Mice lacking βarrestin-2 (βarr2) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of μOR. However, whether abrogating μOR desensitization affects the reinforcing and psychomotor properties of morphine has remained unexplored. In the present study, we examined this question by assessing the effects of morphine and cocaine on locomotor activity, behavioral sensitization, conditioned place preference, and striatal …