Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?

•The opioid system has a key role in modulating neural systems dysregulated in MDD.•Opioids have effects on reward processing and emotional regulation in rodent models.•The impact of opioid ligands on neuroplasticity may suggest antidepressant activity.•Effects mediated by different opioid receptors are complex and context-dependent.•More studies are needed to fill knowledge gaps and identify therapeutic targets.