(R,S)-ketamine, (S)-ketamine, desipramine, MK-801, phencyclidine (PCP) (Sigma-Aldrich, St. Louis, MO, USA), (R)-ketamine (Cayman Chemicals, Ann Arbor, MI, USA) and NBQX (National Institute of Mental Health Chemical Synthesis and Drug Supply Program) were dissolved in 0.9% saline. (2S,6S)-HNK, (2R,6R)-HNK, and 6,6-dideuteroketamine hydrochloride were synthesised and characterised both internally at the National Center for Advancing Translational Sciences and at SRI International (Menlo Park, CA, USA) as described in Supplementary Information. Absolute and relative stereochemistry for (2S,6S)-HNK and (2R,6R)-HNK were confirmed by small molecule x-ray crystallography, as described in the Supplementary Information.
All drugs were dissolved in 0.9% saline, and administered intraperitoneally (i.p.) in a volume of 7.5 ml/kg of body mass by a male experimenter for the behavioural studies. Corticosterone (4-pregnen-11β, 21-diol-3, 20-dione 21-hemisuccinate; Steraloids, Newport, RI, USA) was dissolved in tap water. For the electrophysiology recordings, test drugs were diluted in artificial cerebrospinal fluid (ACSF).