Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: The SHR strain

Author(s)

Almeida, Valeria ^{[1, 2]} ; Peres, Fernanda F. ^{[1, 2]} ; Levin, Raquel ^{[1, 2]} ; Suiama, Mayra A. ^{[1, 2]} ; Calzavara, Mariana B. ^[2] ; Zuardi, Antonio W. ^{[3, 4]} ; Hallak, Jaime E. ^{[3, 4]} ; Crippa, Jose A. ^{[3, 4]} ; Abilio, Vanessa C. ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP EPM, Dept Pharmacol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP EPM, Lab Interdisciplinar Neurociencias Clin LiNC, Dept Psychiat, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Neurosci & Behav, BR-14049 Ribeirao Preto - Brazil

^[4] Natl Inst Translat Med INCT TM, CNPq, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: SCHIZOPHRENIA RESEARCH; v. 153, n. 1-3, p. 150-159, MAR 2014.
• Web of Science Citations: 28

Abstract

Studies have suggested that the endocannabinoid system is implicated in the pathophysiology of schizophrenia. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs display hyperlocomotion - reverted by atypical and typical antipsychotics. These results suggest that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia and the effects of potential drugs with an antipsychotic profile. The aim of this study was to investigate the effects of WIN55-212,2 (CB1/CB2 agonist), ACEA (CB1 agonist), rimonabant (CB1 inverse agonist), AM404 (anandamide uptake/metabolism inhibitor), capsaicin (agonist TRPV1) and capsazepine (antagonist TRPV1) on the social interaction and locomotion of control animals (Wistar rats) and SHRs. The treatment with rimonabant was not able to alter either the social interaction or the locomotion presented by Wistar rats (WR) and SHR at any dose tested. The treatment with WIN55-212,2 decreased locomotion (1 mg/kg) and social interaction (0.1 and 0.3 mg/kg) of WR, while the dose of 1 mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3 mg/kg) and decreased (1 mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5 mg/kg), and decreased social interaction and increased locomotion in WR (1 mg/kg). The treatment with capsaicin (2.5 mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5 mg/kg) and WR (0.5 mg/kg and 2.5 mg/kg). In addition, capsazepine (5 mg/kg) decreased locomotion of both strains and increased (5 mg/kg) and decreased (10 mg/kg) social interaction of WR. Our results indicate that the schizophrenia-like behaviors displayed by SHR are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia. (C) 2014 Elsevier B. V. All rights reserved. (AU)

• FAPESP's process: 10/07994-3 - Role of dopamine and endocannabinoid systems in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR)
• Grantee: Vanessa Costhek Abílio
• Support Opportunities: Regular Research Grants