期刊
NEUROPHARMACOLOGY
卷 146, 期 -, 页码 212-221出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2018.11.035
关键词
Cannabidiol; Cannabinoid CB1 receptor; MAM model; Schizophrenia
资金
- SoMoPro II Programme [3SGA5789]
- project CEITEC 2020 [LQ1601]
- Specific University Research Grant at Masaryk University, Brno, Czechia [MUNI/A/1132/2017]
- Ministry of Education, Youth and Sports of Czech Republic [LO1212]
- Piano triennale per la Ricerca - Linea Intervento 2, University of Catania, Italy [CzBI_IS LM2015062]
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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