Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies.
Pharmacology and Therapeutics July 1, 2019 T. H. Pham, A. Gardier 190 citations
Ketamine produces rapid antidepressant effects in treatment-resistant depression, but the exact mechanisms remain unclear. This review examines evidence that ketamine's fast action involves more than just glutamate release and AMPA receptor activation in the medial prefrontal cortex (mPFC). It also affects GABA, serotonin, glial cells, and circuits connecting the mPFC to the dorsal raphe nucleus. The authors argue that ketamine shifts the excitatory/inhibitory balance in the mPFC and that its metabolites, such as (2R,6R)-HNK, may contribute. They integrate preclinical findings to guide future research on fast-acting antidepressants.