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Opioid Systems and Depression: The Relationship Is Strengthening

  • Merel Dagher
    Affiliations
    Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California
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  • Catherine M. Cahill
    Affiliations
    Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California
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  • Christopher J. Evans
    Correspondence
    Address correspondence to Christopher J. Evans, Ph.D.
    Affiliations
    Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California
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      Prior to the mid-20th century, the acute euphoric effects of opioid drugs and their ability to alleviate depression were primary reasons for physician prescriptions of opioid drugs. This practice was abandoned and discouraged once it was recognized that tolerance, withdrawal, and dependence lead to iatrogenic addiction and opioid use disorder. Nevertheless, the field has far from discarded the connection of the opioid systems with depression [recently reviewed by Jelen et al. (
      • Jelen L.A.
      • Stone J.M.
      • Young A.H.
      • Mehta M.A.
      The opioid system in depression.
      )], including evidence that nonmedical opioid use may precipitate new-onset depressive episodes (
      • Li X.
      • Fu Q.
      • Scherrer J.F.
      • Humphrey D.
      • Leigh I.
      A temporal relationship between nonmedical opioid use and major depression in the U.S.: A prospective study from the National Epidemiological Survey on Alcohol and Related Conditions.
      ). In the current issue of Biological Psychiatry, Carazo-Arias et al. (
      • Carazo-Arias E.
      • Nguyen P.T.
      • Kass M.
      • Jee H.J.
      • Nautiyal K.M.
      • Magalong V.
      • et al.
      Contribution of the opioid system to the antidepressant effects of fluoxetine.
      ) add one more piece to the evolving relationship by implicating the endogenous opioid system in the antidepressant effects of fluoxetine (Figure 1).
      SEE CORRESPONDING ARTICLE ON PAGE 952
      Figure thumbnail gr1
      Figure 1Regulation of fluoxetine by the endogenous opioid system. dHPC, dorsal hippocampus; DOR, delta opioid receptor; KO, knockout; KOR, kappa opioid receptor; MOR, mu opioid receptor; mRNA, messenger RNA; SSRI, selective serotonin reuptake inhibitor; vHPC, ventral hippocampus. Figure created with BioRender.com.
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      Linked Article

      • Contribution of the Opioid System to the Antidepressant Effects of Fluoxetine
        Biological PsychiatryVol. 92Issue 12
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          Selective serotonin reuptake inhibitors such as fluoxetine have a limited treatment efficacy. The mechanism by which some patients respond to fluoxetine while others do not remains poorly understood, limiting treatment effectiveness. We have found the opioid system to be involved in the responsiveness to fluoxetine treatment in a mouse model for anxiety- and depressive-like behavior.
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