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 language | English |
---|---|
Journal | Neuronal Signaling |
Early online date | 18 Apr 2018 |
DOIs | |
Publication status | E-pub ahead of print - 18 Apr 2018 |
Bibliographical note
This was an invited article based on a presentation by SJB at Neuroscience Ireland in 2017.Keywords
- Depression
- Kappa opioid receptor