Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.
Neuropharmacology – November 01, 2024
Source: PubMed
Summary
Ketamine's remarkable dual nature challenges medical understanding - it can both rapidly treat depression and temporarily mimic schizophrenia symptoms. Research reveals this occurs through its interaction with brain NMDA receptors, suggesting these contrasting effects may share underlying mechanisms. Animal studies show ketamine's antidepressant benefits can occur independently of its psychotic-like effects, opening new possibilities for targeted treatments.
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.