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Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors.
- Source :
-
Brain, behavior, and immunity [Brain Behav Immun] 2018 Nov; Vol. 74, pp. 241-251. Date of Electronic Publication: 2018 Sep 11. - Publication Year :
- 2018
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Abstract
- The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms. Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics. The present study investigated if CBD would attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced by chronic administration of haloperidol in mice. Furthermore, we verified in vivo and in vitro (in primary microglial culture) whether these effects would be mediated by PPARγ receptors. The results showed that the male Swiss mice treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily CBD administration before each haloperidol injection prevented this effect. Mice treated with haloperidol showed an increase in microglial activation and inflammatory mediators in the striatum. These changes were also reduced by CBD. On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased in the striatum of animals that received CBD and haloperidol. Regarding oxidative stress, haloperidol induced lipid peroxidation and reduced catalase activity. This latter effect was attenuated by CBD. The combination of CBD and haloperidol also increased PGC-1α mRNA expression, a co-activator of PPARγ receptors. Pretreatment with the PPARγ antagonist, GW9662, blocked the behavioural effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662. In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antioxidants metabolism
Antipsychotic Agents therapeutic use
Behavior, Animal drug effects
Brain metabolism
Cannabidiol metabolism
Corpus Striatum metabolism
Dyskinesia, Drug-Induced metabolism
Dyskinesias drug therapy
Dyskinesias metabolism
Female
Haloperidol pharmacology
Inflammation metabolism
Inflammation pathology
Male
Mice
Mice, Inbred C57BL
Microglia drug effects
Oxidative Stress drug effects
Primary Cell Culture
Superoxide Dismutase metabolism
Tardive Dyskinesia chemically induced
Tardive Dyskinesia drug therapy
Cannabidiol pharmacology
Mastication drug effects
Motor Activity drug effects
PPAR gamma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2139
- Volume :
- 74
- Database :
- MEDLINE
- Journal :
- Brain, behavior, and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 30217539
- Full Text :
- https://doi.org/10.1016/j.bbi.2018.09.014