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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: PHARMACOLOGICAL RESEARCH; v. 156, JUN 2020.
• Web of Science Citations: 0

Abstract

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)

• 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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/17597-3 - The impact of stress on the dopamine system depends on the state of the critical period of neuroplasticity: implications for depression and schizophrenia and for the study of new drug targets
• Grantee: Felipe Villela Gomes
• Support Opportunities: Research Grants - Young Investigators Grants