INTRODUCTION: Dendritic spines are highly plastic structures that determine the strength and efficacy of excitatory synaptic transmission. Chronic elevation of glucocorticoids, such as corticosterone (CORT), disrupts spine morphology and contributes to synaptic dysfunction associated with stress-related disorders. In contrast, ketamine, a rapid-acting antidepressant, has been shown to promote synaptic remodeling and enhance structural plasticity in hippocampal circuits.

AIM(S): Therefore, we investigated whether ketamine reverses morphological alterations induced by chronic CORT exposure in primary mouse hippocampal cultures.

METHOD(S): Primary hippocampal neurons were exposed to CORT (250 nM) for 72 hours to induce stress-related spine remodeling. To assess the potential restorative effects of ketamine, the drug was applied during the final 24 hours of CORT incubation. Spine morphology was subsequently analyzed to evaluate changes in spine length, head width and spine density as these parameters are closely associated with efficacy and maturation of the synapse.

RESULTS: Ketamine treatment showed a tendency to reverse CORT-induced morphological changes. Ketamine restored also spine head dimensions, spine length and density toward control-like values.

CONCLUSIONS: These findings evidenced that ketamine exerts modulatory effects on stress-induced dendritic spine remodeling in hippocampal neurons and may partially counteract glucocorticoid-driven structural impairments. Our results support the hypothesis that ketamine’s rapid antidepressant activity involves mechanisms associated with the restoration of synaptic structural plasticity.

FINANCIAL SUPPORT: Supported by the Polish National Science Center, No. 2021/41/N/NZ4/01845