Pharmacology, biochemistry, and behavior
July 1, 2024
Deren Aykan, Mert Genc, Gunes Unal
8 citations
Combining environmental enrichment with ketamine produces a synergistic antidepressant effect in adult male Wistar rats. Environmental enrichment also reversed spatial memory deficits caused by ketamine in the Morris water maze. Enhanced neuronal activity was observed in the habenula of rats housed in an enriched environment alone after the probe trial, but not in enriched animals that also received ketamine. The findings suggest that sensory-motor stimulation can boost ketamine's antidepressant properties while reducing cognitive side effects, pointing to the potential of pairing pharmacological and environmental interventions for mood disorders.
Psychoneuroendocrinology
July 1, 2025
Ece Idil, Bahar Yuksel, Zeynep Sen et al.
2 citations
Ketamine works faster as an antidepressant in females than in males, and this sex difference has been linked to ovarian hormones and faster metabolism in females. In adult female Wistar rats, blocking estrogen receptor alpha (ERα) with the antagonist MPP before a single antidepressant dose of ketamine did not prevent ketamine from reducing behavioral despair in the forced swim test. ERα antagonism and ketamine together showed a possible interaction on anxiety-like behaviors in the open field and elevated plus maze, but this effect was not statistically significant. Neither treatment affected fear memory. The results indicate that the sex-specific antidepressant effects of ketamine do not depend on ERα activity, though ERα may still influence anxiety-related brain circuits.
Psychopharmacology
June 1, 2025
Bahar Yuksel, Zeynep Sen, Gunes Unal
2 citations
A single antidepressant dose of ketamine (10 mg/kg) given to adult Wistar rats partially impaired fear extinction when administered before fear acquisition or retrieval, but did not affect encoding or retrieval of cued fear or spatial memory. In the Morris Water Maze, ketamine facilitated memory modulation and reduced escape latency during the first day of reversal training when given before training or reversal sessions. The drug did not impair acquisition or retrieval processes in either implicit (fear) or explicit (spatial) memory tasks, but exerted opposing effects on memory modulation: disrupting fear extinction while facilitating reversal spatial learning.
Psychopharmacology
July 1, 2024
Dilan Gokalp, Gunes Unal
Ketamine's antidepressant effect requires suppressed activity of the metabotropic glutamate receptor 5 (mGluR5). In adult male Wistar rats, enhancing mGluR5 activity with the drug CDPPB blocked ketamine's antidepressant effect in the forced swim test without affecting locomotion. Combining a low dose of ketamine (1 mg/kg) with the mGluR5 antagonist MTEP produced a robust synergistic antidepressant effect. However, this combination eliminated the anxiolytic effect seen with either drug alone. The findings indicate that mGluR5 antagonism can boost ketamine's antidepressant effectiveness at low doses, but at the cost of its anxiety-reducing properties.