Cognitive and psychotic effects of ketamine "short- vs. long-term" therapy in a rat model of depression: Hippocampal TrkB/Akt/GSK-3β/mTOR/autophagy trajectories.
Progress in Neuro-psychopharmacology and Biological Psychiatry September 1, 2025 Safaa K Aref, Mohamed Z. Habib, Dalia M. Eid et al. 7 citations
In a rat model of depression, both short-term and long-term ketamine treatment alleviated depressive-like behaviors and normalized stress hormone activity. However, long-term use impaired object recognition memory and increased stereotypic behaviors, indicating potential cognitive and psychotic side effects. Ketamine boosted brain-derived neurotrophic factor (BDNF) and related signaling pathways (TrkB, Akt, GSK-3β, mTOR) while reducing markers of autophagy, tau pathology, and oxidative stress, suggesting enhanced neuronal survival and synaptogenesis. The findings indicate that ketamine's antidepressant benefits come with risks of cognitive decline and psychotic-like effects when used chronically.