Study identifies mu-opioid receptors in prefrontal interneurons as key to ketamine's rapid antidepressant effects

Depression is driven by dysfunction in discrete neural circuits, but a deeper understanding of the underlying molecular and synaptic mechanisms is needed to guide the development of therapeutics.

We decipher the mechanisms of action of the fast-acting antidepressant ketamine to enable the identification of G protein-coupled receptor (GPCR) antidepressant targets.

We find that the behavioral effects of ketamine rely on mu-opioid receptors (MORs), which are enriched in somatostatin-expressing interneurons (Sst+ INs) in the medial prefrontal cortex (mPFC).