Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30496751
DOI
10.1016/j.neuropharm.2018.11.035
PII: S0028-3908(18)30876-1
Knihovny.cz E-resources
- Keywords
- Cannabidiol, Cannabinoid CB1 receptor, MAM model, Schizophrenia,
- MeSH
- Amides MeSH
- Endocannabinoids metabolism MeSH
- Ethanolamines metabolism MeSH
- Glycerides metabolism MeSH
- Hippocampus metabolism MeSH
- Interpersonal Relations MeSH
- Cannabidiol pharmacology MeSH
- Rats MeSH
- Arachidonic Acids metabolism MeSH
- Oleic Acids metabolism MeSH
- Palmitic Acids metabolism MeSH
- RNA, Messenger metabolism MeSH
- Methylazoxymethanol Acetate pharmacology MeSH
- Disease Models, Animal MeSH
- Piperidines pharmacology MeSH
- Motor Activity drug effects MeSH
- Polyunsaturated Alkamides metabolism MeSH
- Prefrontal Cortex metabolism MeSH
- Puberty MeSH
- Pyrazoles pharmacology MeSH
- Receptor, Cannabinoid, CB1 metabolism MeSH
- Recognition, Psychology drug effects MeSH
- Schizophrenia chemically induced drug therapy metabolism MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects drug therapy metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- AM 251 MeSH Browser
- Amides MeSH
- anandamide MeSH Browser
- Endocannabinoids MeSH
- Ethanolamines MeSH
- Glycerides MeSH
- glyceryl 2-arachidonate MeSH Browser
- Cannabidiol MeSH
- Arachidonic Acids MeSH
- Oleic Acids MeSH
- Palmitic Acids MeSH
- RNA, Messenger MeSH
- Methylazoxymethanol Acetate MeSH
- N-oleoylethanolamine MeSH Browser
- palmidrol MeSH Browser
- Piperidines MeSH
- Polyunsaturated Alkamides MeSH
- Pyrazoles MeSH
- Receptor, Cannabinoid, CB1 MeSH
In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic 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.
CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Experimental Medicine and Surgery Tor Vergata University of Rome Rome Italy
Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Physiology Faculty of Medicine Masaryk University Brno Czech Republic
Institute for Drug Research Faculty of Medicine Hebrew University of Jerusalem Jerusalem Israel
Institute of Scientific Instruments Czech Academy of Sciences Brno Czech Republic
References provided by Crossref.org
Prenatal MAM exposure raises kynurenic acid levels in the prefrontal cortex of adult rats
The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
