Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

  • Corey B. Puryear, Alkermes, Inc.
  • ,
  • Julie Brooks, Alkermes, Inc.
  • ,
  • Laura Tan, Alkermes, Inc.
  • ,
  • Karen Smith, Alkermes, Inc.
  • ,
  • Yan Li, Alkermes, Inc.
  • ,
  • Jacobi Cunningham, Alkermes, Inc.
  • ,
  • Mark S. Todtenkopf, Alkermes, Inc.
  • ,
  • Reginald L. Dean, Alkermes, Inc.
  • ,
  • Connie Sanchez

Major depressive disorder (MDD) is a heterogeneous clinical syndrome involving distinct pathological processes. Core features of MDD include anhedonia, reduced motivation, increased anxiety, negative affective bias, cognitive impairments, and dysregulated neuroplasticity mechanisms. There are multiple biological hypotheses related to MDD, including dysfunction of the opioid system. Although opium was abandoned as an antidepressant after the introduction of monoaminergic drugs, there has been renewed interest in targeting the opioid system for MDD. In this review, we discuss the preclinical support of this idea using a neurocircuitry- and molecular neuroplasticity-based approach. This article highlights how the opioid system potently modulates mesolimbic circuitry underlying motivation and reward processing, limbic circuitry underlying fear and anxiety responses, cortical and hippocampal circuitry underlying a variety of cognitive functions, as well as broad functional and structural plasticity mechanisms. Ultimately, a more thorough understanding of how the opioid system modulates these core functional domains may lead to novel treatment strategies and molecular targets in the treatment of MDD.

Original languageEnglish
JournalNeuroscience and Biobehavioral Reviews
Volume108
Pages (from-to)658-678
Number of pages21
ISSN0149-7634
DOIs
Publication statusPublished - Jan 2020

    Research areas

  • Cognition, Major depressive disorder, Negative valence, Neural circuits, Neuroplasticity, Opioid receptors, Opioid system, Positive valence, Research domain criterion (RDoC)

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