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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 \u03ba 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 \u03bc 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.<\/jats:p>","DOI":"10.1042\/ns20170145","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T12:10:34Z","timestamp":1524053434000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Targeting opioid receptor signaling in depression: do we need selective \u03ba opioid receptor antagonists?"],"prefix":"10.1042","volume":"2","author":[{"given":"Sarah\u00a0J.","family":"Bailey","sequence":"first","affiliation":[{"name":"Drug and Target Discovery, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen\u00a0M.","family":"Husbands","sequence":"additional","affiliation":[{"name":"Drug and Target Discovery, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,5,14]]},"reference":[{"issue":"Suppl. 1","key":"2021111608014652900_B1","doi-asserted-by":"publisher","first-page":"S153","DOI":"10.1038\/sj.bjp.0706435","article-title":"75 years of opioid research: the exciting but vain quest for the Holy Grail","volume":"147","author":"Corbett","year":"2006","journal-title":"Br. 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