Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.
M C Acero-Castillo, M B M Correia, F V Caixeta, V Motta, M Barros, R S Maior
Neuropharmacology November 1, 2024 DOI: 10.1016/j.neuropharm.2024.110088 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Ketamine Esketamine |
| Keywords | Nmda Schizophrenia Psychopharmacology Mental health research Antidepressants Drug mechanisms |
| Citations | 7 |
| Key findings | Ketamine at subanesthetic doses acts both as a fast-acting antidepressant and as a pharmacological model of schizophrenia, with its dual effects arising from NMDA receptor mechanisms. |
Abstract
Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.