Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors
| Autor: | Gabriel T. do Vale, Douglas Silva Prado, Thiago M. Cunha, Rita Raisman-Vozari, Elaine Aparecida Del Bel, Andreza B. Sonego, Francisco Silveira Guimarães, Carlos R. Tirapelli, Julia E. Sepulveda-Diaz |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Dyskinesia Drug-Induced medicine.medical_treatment Striatum Pharmacology medicine.disease_cause Antioxidants Mice Behavioral Neuroscience 0302 clinical medicine Haloperidol Cannabidiol Receptor Behavior Animal ESTRESSE OXIDATIVO Brain surgical procedures operative Female Microglia medicine.symptom Antipsychotic Agents medicine.drug Primary Cell Culture Immunology Motor Activity Tardive dyskinesia 03 medical and health sciences medicine Animals Tardive Dyskinesia Antipsychotic Inflammation Dyskinesias Superoxide Dismutase Endocrine and Autonomic Systems business.industry medicine.disease Corpus Striatum digestive system diseases Mice Inbred C57BL PPAR gamma Oxidative Stress 030104 developmental biology Dyskinesia Mastication business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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