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

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:108

Review

Puryear, Corey B.¹  Brooks, Julie¹  Tan, Laura¹  Smith, Karen¹  Li, Yan¹  Cunningham, Jacobi¹  Todtenkopf, Mark S.¹  Dean, Reginald L.¹  Sanchez, Connie^1,2 

[1] Alkermes Inc, 852 Winter St, Waltham, MA 02451 USA

[2] Aarhus Univ, Translat Neuropsychiat Unit, Clin Med, Skovagervej 2, DK-8240 Risskov, Denmark

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

DOI  :  10.1016/j.neubiorev.2019.12.007

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free