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Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia

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ŠTARK Tibor RUDÁ Jana IANNOTI Fabio D'ADDARIO Claudio DI MARCO Roberta PEKAŘÍK Vladimír DRAŽANOVÁ Eva PISCITELLI Fabiana BARI Monica BABINSKÁ Zuzana GIURDANELLA Giovanni DI BARTOLOMEO Martina SALOMONE Salvatore ŠULCOVÁ Alexandra MACCARRONE Mauro WOTJAK Carsten STARČUK Zenon DRAGO Filippo MECHOULAM Raphael DI MARZO Vincenzo MICALE Vincenzo

Druh Článek v odborném periodiku
Časopis / Zdroj Neuropharmacology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
WWW https://www.sciencedirect.com/science/article/pii/S0028390818308761
Doi http://dx.doi.org/10.1016/j.neuropharm.2018.11.035
Klíčová slova Cannabidiol; Cannabinoid CB1 receptor; MAM model; Schizophrenia
Popis In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the anti mitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.
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