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Brain NMDA Receptors in Schizophrenia and Depression

by Albert Adell 1,2
Institute of Biomedicine and Biotechnology of Cantabria, IBBTEC (CSIC-University of Cantabria), Calle Albert Einstein 22 (PCTCAN), 39011 Santander, Spain
Biomedical Research Networking Center for Mental Health (CIBERSAM), 39011 Santander, Spain
Biomolecules 2020, 10(6), 947;
Received: 3 June 2020 / Revised: 19 June 2020 / Accepted: 21 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue NMDA Receptor in Health and Diseases)
N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP), dizocilpine (MK-801) and ketamine have long been considered a model of schizophrenia, both in animals and humans. However, ketamine has been recently approved for treatment-resistant depression, although with severe restrictions. Interestingly, the dosage in both conditions is similar, and positive symptoms of schizophrenia appear before antidepressant effects emerge. Here, we describe the temporal mechanisms implicated in schizophrenia-like and antidepressant-like effects of NMDA blockade in rats, and postulate that such effects may indicate that NMDA receptor antagonists induce similar mechanistic effects, and only the basal pre-drug state of the organism delimitates the overall outcome. Hence, blockade of NMDA receptors in depressive-like status can lead to amelioration or remission of symptoms, whereas healthy individuals develop psychotic symptoms and schizophrenia patients show an exacerbation of these symptoms after the administration of NMDA receptor antagonists. View Full-Text
Keywords: NMDA; depression; schizophrenia; subunit; glutamate; GABA NMDA; depression; schizophrenia; subunit; glutamate; GABA
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Adell, A. Brain NMDA Receptors in Schizophrenia and Depression. Biomolecules 2020, 10, 947.

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