Mice deficient for delta- and gamma-opioid receptors exhibit opposing alterations of emotional responses

The role of the opioid system in controlling pain(1), reward and addidion(2 ,3) is well established, but its role in regulating other emotional respons es is poorly documented in pharmacology(4). The mu-. delta- and kappa- opio id receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the b iological activity of opioids(5) We have generated Oprd1-deficient mice and compared the behavioural responses of mice lacking Oprd1, Oprm (ref. 6) an d Oprk1 (ref. 7) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1(-/-) mutants. suggesting that ic-receptor s do not have a role in this aspect of opioid function; opposing phenotypes in Oprm(-/-) and Oprd1(-/-) mutants which contrasts with the classical not ion of similar activities of mu-and delta-receptors; and consistent anxioge nic- and depressive-like responses in Oprd1(-/-) mice, indicating that delt a-receptor activity contributes to improvement of mood states. We conclude that the Oprdl-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.