Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats.

Autor: Brakatselos C; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Polissidis A; Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.; Department of Science and Mathematics, ACG-Research Center, Deree - American College of Greece, 15342, Athens, Greece., Ntoulas G; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Asprogerakas MZ; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Tsarna O; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Vamvaka-Iakovou A; Institute of Biosciences & Applications, NCSR Demokritos, Athens, Greece.; Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal., Nakas G; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Delis A; Center of Basic Research, Biological Imaging Unit, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece., Tzimas P; Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771, Athens, Greece., Skaltsounis L; Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771, Athens, Greece., Silva J; Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal., Delis F; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece., Oliveira JF; Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.; IPCA-EST-2Ai, Polytechnic Institute of Cávado and Ave, Applied Artificial Intelligence Laboratory, Campus of IPCA, Barcelos, Portugal., Sotiropoulos I; Institute of Biosciences & Applications, NCSR Demokritos, Athens, Greece.; Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal., Antoniou K; Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece. kantoniou@uoi.gr.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Sep 06. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1038/s41386-024-01977-1
Abstrakt: Repeated administration of ketamine (KET) has been used to model schizophrenia-like symptomatology in rodents, but the psychotomimetic neurobiological and neuroanatomical underpinnings remain elusive. In parallel, the unmet need for a better treatment of schizophrenia requires the development of novel therapeutic strategies. Cannabidiol (CBD), a major non-addictive phytocannabinoid has been linked to antipsychotic effects with unclear mechanistic basis. Therefore, this study aims to clarify the neurobiological substrate of repeated KET administration model and to evaluate CBD's antipsychotic potential and neurobiological basis. CBD-treated male rats with and without prior repeated KET administration underwent behavioral analyses, followed by multilevel analysis of different brain areas including dopaminergic and glutamatergic activity, synaptic signaling, as well as electrophysiological recordings for the assessment of corticohippocampal and corticostriatal network activity. Repeated KET model is characterized by schizophrenia-like symptomatology and alterations in glutamatergic and dopaminergic activity mainly in the PFC and the dorsomedial striatum (DMS), through a bi-directional pattern. These observations are accompanied by glutamatergic/GABAergic deviations paralleled to impaired function of parvalbumin- and cholecystokinin-positive interneurons, indicative of excitation/inhibition (E/I) imbalance. Moreover, CBD counteracted the schizophrenia-like behavioral phenotype as well as reverted prefrontal abnormalities and ventral hippocampal E/I deficits, while partially modulated dorsostriatal dysregulations. This study adds novel insights to our understanding of the KET-induced schizophrenia-related brain pathology, as well as the CBD antipsychotic action through a region-specific set of modulations in the corticohippocampal and costicostrtiatal circuitry of KET-induced profile contributing to the development of novel therapeutic strategies focused on the ECS and E/I imbalance restoration.
(© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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