Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology December 1, 2024 Charalampos Brakatselos, Alexia Polissidis, George Ntoulas et al. 10 citations
Repeated ketamine administration in male rats produces schizophrenia-like symptoms and alters glutamatergic and dopaminergic activity, mainly in the prefrontal cortex and dorsomedial striatum, through a bidirectional pattern. These changes are accompanied by glutamatergic/GABAergic deviations and impaired function of parvalbumin- and cholecystokinin-positive interneurons, indicating an excitation/inhibition imbalance. Cannabidiol (CBD) counteracted the schizophrenia-like behavioral phenotype, reversed prefrontal abnormalities and ventral hippocampal E/I deficits, and partially modulated dorsostriatal dysregulations. The findings suggest CBD's antipsychotic action involves region-specific modulations in corticohippocampal and corticostriatal circuitry, pointing to potential therapeutic strategies focused on restoring E/I balance.