Enhanced morphine analgesia in mice lacking beta-arrestin 2

The ability of morphine to alleviate pain is mediated through a heterotrime ric guanine nucleotide binding protein (G protein)-coupled heptahelical rec eptor (GPCR), the mu opioid receptor (mu OR). The efficiency of GPCR signal ing is tightly regulated and ultimately Limited by the coordinated phosphor ylation of the receptors by specific GPCR kinases and the subsequent intera ction of the phosphorylated receptors with beta-arrestin 1 and beta-arresti n 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in re markable potentiation and prolongation of the analgesic effect of morphine, suggesting that mu OR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in reg ulating the function of a specific GPCR, the mu OR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesi c effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence.