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

https://doi.org/10.1016/j.neubiorev.2019.12.007Get rights and content
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open access

Highlights

  • The opioid system has a key role in modulating neural systems dysregulated in MDD.

  • Opioids have effects on reward processing and emotional regulation in rodent models.

  • The impact of opioid ligands on neuroplasticity may suggest antidepressant activity.

  • Effects mediated by different opioid receptors are complex and context-dependent.

  • More studies are needed to fill knowledge gaps and identify therapeutic targets.

Abstract

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.

Keywords

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

Cited by (0)

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Equal contributions.