NADPH oxidase-1 suppression prolongs the antidepressant-like effect of ketamine.
Molecular psychiatry July 1, 2026 Waki Nakajima, Tetsu Arisawa, Susumu Jitsuki et al. 1 citation
A novel compound, K-4, which positively modulates AMPA receptors, produced longer-lasting antidepressant-like effects in a rat model of treatment-resistant depression than ketamine alone. K-4 reduced expression of the enzyme NOX-1 in the medial prefrontal cortex. Blocking NOX-1, either with an inhibitor or by genetic knockdown, prolonged ketamine's antidepressant-like effects and reduced abnormal bursting in the lateral habenula, a brain region linked to depression. Suppressing NOX-1 may be a promising strategy for extending the benefits of ketamine in treatment-resistant depression.