Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors

Autor(es)

da Silva, Naielly Rodrigues ^[1] ; Gomes, Felipe Villela ^[1] ; Sonego, Andreza Buzolin ^[1] ; da Silva, Nicole Rodrigues ^[1] ; Guimaraes, Francisco Silveira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL RESEARCH; v. 156, JUN 2020.
• Citações Web of Science: 0

Resumo

Preclinical and clinical data indicate that cannabidiol (CBD), a non-psychotomimetic compound from the Cannabis saliva plant, can induce antipsychotic-like effects. In an animal model of schizophrenia based on the antagonism of NMDA receptors, the behavioral and molecular changes induced by repeated treatment with the NMDA receptor antagonist MK-801 were prevented when CBD was co-administered with MK-801. It is unknown, however, if CBD would reverse these changes once they have been established. Thus, in the present study we used male C57BL/6J mice, 6 weeks old, to evaluate whether daily CBD injection for seven days, starting after the end of the repeated treatment with MK-801 for 14 days, would reverse MK-801-induced deficits in the social interaction (SI) and novel object recognition (NOR) tests, which have been used to investigate the negative and cognitive symptoms of schizophrenia, respectively. We also assessed whether CBD effects would be blocked by pretreatment with AM251, a CB1 receptor antagonist, AM630, a CB2 receptor antagonist, or WAY100635, a 5-HT1A receptor antagonist. CBD and the second-generation antipsychotic clozapine, used as a positive control, attenuated the impairments in the SI and NOR tests induced by repeated administered MK-801. CBD effects were blocked by WAY100635, but not by AM251 or AM630. These data suggest that CBD induces antipsychotic-like effects by activating 5-HT1A receptors and indicate that this compound could be an interesting alternative for the treatment of negative and cognitive symptoms of schizophrenia. (AU)

• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/17597-3 - O impacto do estresse sobre o sistema dopaminérgico é determinado pelo período crítico de plasticidade: implicações para a depressão e a esquizofrenia e o estudo de novos alvos farmacológicos
• Beneficiário: Felipe Villela Gomes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores