Mice deficient for δ- and μ-opioid receptors exhibit opposing alterations of emotional responses

The role of the opioid system in controlling pain 1 , reward and addiction 2 , 3 is well established, but its role in regulating other emotional responses is poorly documented in pharmacology 4 . The μ-, δ- and κ- opioid receptors (encoded by Oprm, Oprd1 and Oprk1 , respectively) mediate the biological activity of opioids 5 . We have generated Oprd1 -deficient mice and compared the behavioural responses of mice lacking Oprd1 , Oprm (ref. 6 ) and Oprk1 (ref. 7 ) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1 −/− mutants, suggesting that κ-receptors do not have a role in this aspect of opioid function; opposing phenotypes in Oprm −/− and Oprd1 −/− mutants which contrasts with the classical notion of similar activities of μ- and δ-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1 −/− mice, indicating that δ-receptor activity contributes to improvement of mood states. We conclude that the Oprd1 -encoded receptor, which has been proposed to be a promising target for the clinical management of pain 8 , 9 , should also be considered in the treatment of drug addiction and other mood-related disorders.