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Review
. 2018 May 14;2(2):NS20170145.
doi: 10.1042/NS20170145. eCollection 2018 Jun.

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Affiliations
Review

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Sarah J Bailey et al. Neuronal Signal. .

Abstract

The opioid receptors are a family of G-protein coupled receptors (GPCRs) with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally β-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focused on the development of analgesics. However, more recent attention has turned to the role of central opioid receptors in the regulation of stress responses, anhedonia and mood. Activation of the κ opioid receptor (KOP) subtype has been shown in both human and rodent studies to produce dysphoric and pro-depressive like effects. This has led to the idea that selective KOP antagonists might have therapeutic potential as antidepressants. Here we review data showing that mixed μ opioid (MOP) and KOP antagonists have antidepressant-like effects in rodent behavioural paradigms and highlight comparable studies in treatment-resistant depressed patients. We propose that developing multifunctional ligands which target multiple opioid receptors open up the potential for fine-tuning hedonic responses mediated by opioids. This alternative approach towards targeting multiple opioid receptors may lead to more effective treatments for depression.

Keywords: antidepressants; depression; opioid receptors.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Opioid receptors regulate hedonic tone
The opioid receptors MOP, DOP and KOP have all been implicated in the control of hedonic tone. The above diagram illustrates how the balance of activation of these receptors could contribute to overall hedonic tone. Agonist activation of MOP and DOP receptors is proposed to increase hedonic tone whereas activation of KOP receptors produces anhedonia. Blockade of both KOP and MOP receptors by BU10119, buprenorphine, naltrexone, 5′-AMN and 5′-MABN produced antidepressant-like responses in rodents, perhaps by rebalancing hedonic tone.

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References

    1. Corbett A.D., Henderson G., McKnight A.T. and Paterson S.J. (2006) 75 years of opioid research: the exciting but vain quest for the Holy Grail. Br. J. Pharmacol. 147 (Suppl. 1), S153–S162 10.1038/sj.bjp.0706435 - DOI - PMC - PubMed
    1. Van’t Veer A. and Carlezon W. Jr (2013) Role of kappa-opioid receptors in stress and anxiety-related behavior. Psychopharmacology (Berl.) 229, 435–452 10.1007/s00213-013-3195-5 - DOI - PMC - PubMed
    1. Lutz P.-E. and Kieffer B.L. (2013) Opioid receptors: distinct roles in mood disorders. Trends Neurosci. 36, 195–206 10.1016/j.tins.2012.11.002 - DOI - PMC - PubMed
    1. Carroll F.I. and Carlezon W.A. (2013) Development of κ opioid receptor antagonists. J. Med. Chem. 56, 2178–2195 10.1021/jm301783x - DOI - PMC - PubMed
    1. Toll L., Caló G., Cox B.M., Chavkin C., Christie M.J., Civelli O. et al. . (2017) Opioid receptors. In IUPHAR/BPS Guide to Pharmacology, http://www.guidetopharmacologyorg/GRAC/FamilyDisplayForward?familyId=50