The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions.

"supplementary table s1 ). all tests are two-sided. all data"

"Competing interests RSD consulted and/or received research support from Allergan, Naurex, Aptinyx, Sunovian, Eli Lilly, Johnson & Johnson, Taisho, Relmada, and Navitor. CP serves as a consultant and/or receives research support from Biohaven Pharmaceuticals, Ceruvia Lifesciences, Freedom Biosciences, Transcend Therapeutics, Nobilis Therapeutics, UCB BioPharma, Teva Pharmaceuticals, Lundbeck Therapeutics, and F-Prime Capital Partners. He owns equity in Alco Therapeutics, receives royalties and/or honoraria from Oxford University Press, Elsevier, and Up-To-Date, and has filed a patent on the use of psilocybin in the treatment of OCD, irrelevant to the current work. CJ and RJD report no biomedical financial interests or potential conflicts of interest."

"Funding This research was supported by the National Institutes of Health (grants MH093897 to RSD and RJD, NS101104 and MH127259 to CP, Yale/National Institute on Drug Abuse (NIDA) Neuroproteomics Center Pilot Research Project Grant through DA018343 to CJ) and a Tourette Association of America Young Investigator Award (CJ). This work was partially funded by the State of Connecticut, Department of Mental Health and Addiction Services, but this publication does not express the views of the Department of Mental Health and Addiction Services or the State of Connecticut. The views and opinions expressed are those of the authors."