Mice deficient for delta- and mu-opioid receptors
exhibit opposing alterations of emotional responses
by
Filliol D, Ghozland S, Chluba J, Martin M, Matthes HW,
Simonin F, Befort K, Gaveriaux-Ruff C, Dierich A,
LeMeur M, Valverde O, Maldonado R, Kieffer BL
[1] UPR 9050 CNRS,
ESBS Universite Louis Pasteur,
Illkirch,
Strasbourg,
France.
[2] These authors contributed equally to this work.
Nat Genet 2000 Jun; 25(2):195-200

ABSTRACT

The role of the opioid system in controlling pain, reward and addiction is well established, but its role in regulating other emotional responses is poorly documented in pharmacology. The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids. 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 kappa-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 mu- and delta-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1-/- mice, indicating that delta-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, should also be considered in the treatment of drug addiction and other mood-related disorders.

Mu
CREB
The delta connection
Fentanyl and ketamine
Dynorphin and dopamine
Kappa upregulation and addiction
Opioids, brain stimulation and reward
Delta opioid receptors, emotion and motivation
Delta-opioid receptor agonists as antidepressants?
Happiness, sadness and mu-opioid neurotransmission

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