NEUROBIOLOGICAL MECHANISMS OF KETAMINE IN THE TREATMENT OF RESISTANT DEPRESSION: THE ROLE OF GLUTAMATERGIC NEUROTRANSMISSION AND NEUROPLASTICITY

Abstract

This article sought to analyze the neurobiological mechanisms involved in the rapid antidepressant effect of ketamine in patients with treatment-resistant depression, with an emphasis on glutamatergic neurotransmission and neuroplasticity. This is a qualitative study of a theoretical-bibliographic nature and with an analytical-reflective approach, based on the analysis of scientific articles and academic publications related to the use of ketamine and the mechanisms associated with the antidepressant response. The study considered aspects related to NMDA and AMPA receptors, brain-derived neurotrophic factor (BDNF), the mTOR pathway, synaptic plasticity, and the brain circuits involved in mood regulation. The results showed that ketamine modulates NMDA receptors, promoting glutamatergic neurotransmission mediated by AMPA receptors and triggering changes in BDNF-TrkB and mTOR signaling. These mechanisms contribute to increased synaptic plasticity and rapid remodeling of neuronal connections, which are associated with an improvement in depressive symptoms. It is concluded that ketamine’s rapid antidepressant action is related to the interaction between glutamatergic neurotransmission and neuroplasticity mechanisms, highlighting its therapeutic potential in treatment-resistant depression.