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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

annabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatu

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Pedrazzi, Joao F. C. [1] ; Sales, Amanda J. [2] ; Guimaraes, Francisco S. [2] ; Joca, Samia R. L. [3, 4] ; Crippa, Jose A. S. [1] ; Del Bel, Elaine [5]
Total Authors: 6
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Neurosci & Behav Sci, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil
[3] Aarhus Univ, Dept Biomed, Aarhus - Denmark
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Biomol Sci, Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 1

Cannabidiol (CBD), a major non-psychotomimetic component of the Cannabis sativa plant, shows therapeutic potential in several psychiatric disorders, including schizophrenia. The molecular mechanisms underlying the antipsychotic-like effects of CBD are not fully understood. Schizophrenia and antipsychotic treatment can modulate DNA methylation in the blood and brain, resulting in altered expression of diverse genes associated with this complex disorder. However, to date, the possible involvement of DNA methylation in the antipsychoticlike effects of CBD has not been investigated. Therefore, this study aimed at evaluating in mice submitted to the prepulse inhibition (PPI) model: i) the effects of a single injection of CBD or clozapine followed by AMPH or MK801 on PPI and global DNA methylation changes in the ventral striatum and prefrontal cortex (PFC); and ii). if the acute antipsychotic-like effects of CBD would last for 24-h. AMPH (5 mg/kg) and MK-801 (0.5 mg/kg) impaired PPI. CBD (30 and 60 mg/kg), similar to clozapine (5 mg/kg), attenuated AMPH- and MK801-induced PPI disruption. AMPH, but not MK-801, increased global DNA methylation in the ventral striatum, an effect prevented by CBD. CBD and clozapine increased, by themselves, DNA methylation in the prefrontal cortex. The acute effects of CBD (30 or 60 mg/kg) on the PPI impairment induced by AMPH or MK-801 was also detectable 24 h later. Altogether, the results show that CBD induces acute antipsychotic-like effects that last for 24-h. It also modulates DNA methylation in the ventral striatum, suggesting a new potential mechanism for its antipsychoticlike effects. (AU)

FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/06515-8 - Mechanisms involved in the cannabidiol antipsychotic profile
Grantee:João Francisco Cordeiro Pedrazzi
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia
Grantee:Elaine Aparecida Del Bel Belluz Guimarães
Support type: Research Projects - Thematic Grants