Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?. (January 2020)

• Record Type: Journal Article
• Authors: Puryear, Corey B.; Brooks, Julie; Tan, Laura; Smith, Karen; Li, Yan; Cunningham, Jacobi; Todtenkopf, Mark S.; Dean, Reginald L.; Sanchez, Connie
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 108(2020)
• Page Start: 658
• Page End: 678
• Publication Date: 2020-01
• Subjects: Major depressive disorder -- Positive valence -- Negative valence -- Cognition -- Neuroplasticity -- Opioid system -- Opioid receptors -- Neural circuits -- Research domain criterion (RDoC); Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2019.12.007
• Languages: English
• ISSNs: 0149-7634

Abstract

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.