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

Research output: Contribution to journalArticle

Abstract

The opioid receptors are a family of G-protein coupled receptors with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally b-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focussed 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 kappa 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 mu 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 opens 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.
Original languageEnglish
JournalNeuronal Signaling
Early online date18 Apr 2018
DOIs
Publication statusE-pub ahead of print - 18 Apr 2018

Fingerprint

kappa Opioid Receptor
Narcotic Antagonists
Opioid Receptors
Depression
Opioid Analgesics
Antidepressive Agents
Rodentia
Anhedonia
Endorphins
Leucine Enkephalin
Dynorphins
Methionine Enkephalin
Pleasure
G-Protein-Coupled Receptors
Neuropeptides
Analgesics
Therapeutics
Ligands

Keywords

  • Depression
  • Kappa opioid receptor

Cite this

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title = "Targeting opioid receptor signaling in depression: do we need selective kappa opioid receptor antagonists?",
abstract = "The opioid receptors are a family of G-protein coupled receptors with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally b-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focussed 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 kappa 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 mu 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 opens 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 = "Depression, Kappa opioid receptor",
author = "Sarah Bailey and Stephen Husbands",
note = "This was an invited article based on a presentation by SJB at Neuroscience Ireland in 2017.",
year = "2018",
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doi = "10.1042/NS20170145",
language = "English",
journal = "Neuronal Signaling",
issn = "2059-6553",
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AU - Bailey, Sarah

AU - Husbands, Stephen

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Y1 - 2018/4/18

N2 - The opioid receptors are a family of G-protein coupled receptors with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally b-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focussed 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 kappa 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 mu 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 opens 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.

AB - The opioid receptors are a family of G-protein coupled receptors with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally b-endorphin, dynorphins, leu- and met-enkephalins. The clinical potential of targeting opioid receptors has largely focussed 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 kappa 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 mu 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 opens 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.

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