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

dc.contributor.authorLevin, Raquel [UNIFESP]
dc.contributor.authorPeres, Fernanda Fiel [UNIFESP]
dc.contributor.authorAlmeida, Valeria [UNIFESP]
dc.contributor.authorCalzavara, Mariana Bendlin [UNIFESP]
dc.contributor.authorZuardi, Antonio W.
dc.contributor.authorHallak, Jaime E. C.
dc.contributor.authorCrippa, Jose Alexandre S.
dc.contributor.authorAbilio, Vanessa Costhek [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionNatl Council Sci & Technol Dev
dc.date.accessioned2016-01-24T14:35:18Z
dc.date.available2016-01-24T14:35:18Z
dc.date.issued2014-02-06
dc.description.abstractClinical 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.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Neurosci & Behav, BR-14049 Ribeirao Preto, Brazil
dc.description.affiliationNatl Council Sci & Technol Dev, Natl Inst Sci & Technol Translat Med, Ribeirao Preto, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: FAPESP - 2010/07994-3
dc.format.extent10
dc.identifierhttp://dx.doi.org/10.3389/fphar.2014.00010
dc.identifier.citationFrontiers in Pharmacology. Lausanne: Frontiers Research Foundation, v. 5, 10 p., 2014.
dc.identifier.doi10.3389/fphar.2014.00010
dc.identifier.fileWOS000347041400001.pdf
dc.identifier.issn1663-9812
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37432
dc.identifier.wosWOS:000347041400001
dc.language.isoeng
dc.publisherFrontiers Research Foundation
dc.relation.ispartofFrontiers in Pharmacology
dc.rightsAcesso aberto
dc.subjectschizophreniaen
dc.subjectSHRen
dc.subjectPPIen
dc.subjectcannabinoid drugsen
dc.subjectanimal modelen
dc.titleEffects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strainen
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