Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

Author(s)

Gomes, Felipe V. ^{[1, 2]} ; Llorente, Ricardo ^[3] ; Del Bel, Elaine A. ^{[1, 4]} ; Viveros, Maria-Paz ^[5] ; Lopez-Gallardo, Meritxell ^[3] ; Guimaraes, Francisco S. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Complutense Madrid, Fac Med, Dept Physiol, E-28040 Madrid - Spain

^[4] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Complutense Madrid, Fac Biol, Dept Physiol Anim Physiol 2, E-28040 Madrid - Spain

• Document type: Journal article
• Source: SCHIZOPHRENIA RESEARCH; v. 164, n. 1-3, p. 155-163, MAY 2015.
• Web of Science Citations: 41

Abstract

NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal that CBD may induce antipsychotic-like effects. Although the possible mechanism of action of these effects is still unknown, it may involve CBD anti-inflammatory and neuroprotective properties. Furthermore, our data support the view that inhibition of microglial activation may improve schizophrenia symptoms. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/14144-1 - Evaluation of the involvement of neuronal and glial changes in the antipsychotic properties of cannabidiol
• Grantee: Felipe Villela Gomes
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 10/17343-0 - Evaluation of CBD effects on the molecular and behavioral changes induced by repeated treatment with MK-801
• Grantee: Felipe Villela Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate