title: Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain.
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). Wistar rats (WRs) 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 WRs. 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.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil ; Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Levin
authors.affiliation: Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil ; Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Peres
authors.affiliation: Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil ; Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Valéria
authors.initials: V
authors.lastname: Almeida
authors.affiliation: Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Mariana B
authors.initials: MB
authors.lastname: Calzavara
authors.affiliation: Department of Neuroscience and Behavior, University of São Paulo Ribeirão Preto, Brazil ; National Institute of Science and Technology in Translational Medicine, National Council for Scientific and Technological Development Ribeirão Preto, Brazil.
authors.forename: Antonio W
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: Department of Neuroscience and Behavior, University of São Paulo Ribeirão Preto, Brazil ; National Institute of Science and Technology in Translational Medicine, National Council for Scientific and Technological Development Ribeirão Preto, Brazil.
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
authors.affiliation: Department of Neuroscience and Behavior, University of São Paulo Ribeirão Preto, Brazil ; National Institute of Science and Technology in Translational Medicine, National Council for Scientific and Technological Development Ribeirão Preto, Brazil.
authors.forename: José Alexandre S
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil ; Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Abílio
keywords: PPI; SHR; animal model; cannabinoid drugs; schizophrenia