Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

Author Levin, Raquel Autor UNIFESP Google Scholar
Peres, Fernanda Fiel Autor UNIFESP Google Scholar
Almeida, Valeria Autor UNIFESP Google Scholar
Calzavara, Mariana Bendlin Autor UNIFESP Google Scholar
Zuardi, Antonio W. Google Scholar
Hallak, Jaime E. C. Google Scholar
Crippa, Jose Alexandre S. Google Scholar
Abilio, Vanessa Costhek Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Natl Council Sci & Technol Dev
Abstract Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. the aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. the following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). VVistar rats (VVRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to VVRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.
Keywords schizophrenia
SHR
PPI
cannabinoid drugs
animal model
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: FAPESP - 2010/07994-3
Date 2014-02-06
Published in Frontiers in Pharmacology. Lausanne: Frontiers Research Foundation, v. 5, 10 p., 2014.
ISSN 1663-9812 (Sherpa/Romeo, impact factor)
Publisher Frontiers Research Foundation
Extent 10
Origin http://dx.doi.org/10.3389/fphar.2014.00010
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000347041400001
URI http://repositorio.unifesp.br/handle/11600/37432

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