Journal of neuroscience research
April 1, 2022
Emilija Glavonic, Milos Mitic, Miroslav Adzic
20 citations
Fear-related disorders like phobias and PTSD involve disrupted fear extinction, leading to excessive fear. Exposure therapy, the standard treatment, fails in up to 35% of patients, and adding antidepressants offers no extra benefit. Hallucinogenic drugs, particularly MDMA and ketamine, may enhance therapy by promoting neuroplastic changes in fear circuits and reducing amygdala hyperreactivity. This review examines preclinical and clinical evidence showing these drugs can strengthen fear extinction learning and improve emotional engagement in psychotherapy, potentially outperforming current first-line treatments.
Journal of neuroscience research
January 1, 2024
Chitra Vinnakota, Anna Schroeder, Xin Du et al.
7 citations
Blocking NMDA receptors with drugs like PCP and ketamine causes psychosis-like symptoms in humans and hyperlocomotion in rodents. Mice lacking the GluN2D subunit of the NMDA receptor show reduced hyperlocomotion in response to these drugs, suggesting this subunit is key for that effect. This study tested male and female mice lacking GluN2D and found they also had blunted locomotor responses to PCP, S-ketamine, and R-norketamine, in both sexes. These knockout mice showed an anxious baseline, and the drugs had anxiolytic effects that varied by sex and genotype. S-ketamine disrupted spatial memory in females and object recognition in both sexes, regardless of genotype. The GluN2D subunit mediates sex-specific and drug-specific behavioral effects of NMDA receptor antagonists.
Journal of neuroscience research
January 1, 2026
Stephanie Njau, Artemis Zavaliangos-Petropulu, Shantanu Joshi et al.
In people with treatment-resistant depression, a single low-dose ketamine infusion increased glutamate levels in the dorsal anterior cingulate cortex only in those who responded to treatment, and lower pre-treatment glutamate levels predicted greater improvement in depression scores. GABA levels did not change after treatment. Other brain metabolites linked to neuronal health and metabolism also increased. These findings suggest that ketamine's antidepressant effect involves sustained enhancement of glutamate-related neurotransmission and that baseline glutamate levels may help predict who will benefit from ketamine.