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

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