title: Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: the SHR strain.
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 (1mg/kg) and social interaction (0.1 and 0.3mg/kg) of WR, while the dose of 1mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3mg/kg) and decreased (1mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5mg/kg), and decreased social interaction and increased locomotion in WR (1mg/kg). The treatment with capsaicin (2.5mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5mg/kg) and WR (0.5mg/kg and 2.5mg/kg). In addition, capsazepine (5mg/kg) decreased locomotion of both strains and increased (5mg/kg) and decreased (10mg/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.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, UNIFESP/EPM, Brazil; Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, Brazil.
authors.forename: Valéria
authors.initials: V
authors.lastname: Almeida
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, UNIFESP/EPM, Brazil; Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, Brazil.
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Peres
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, UNIFESP/EPM, Brazil; Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Levin
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, UNIFESP/EPM, Brazil; Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, Brazil.
authors.forename: Mayra A
authors.initials: MA
authors.lastname: Suiama
authors.affiliation: Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, 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 for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
authors.forename: Antônio W
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: Department of Neuroscience and Behavior, University of São Paulo, Ribeirão Preto, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hallak
authors.affiliation: Department of Neuroscience and Behavior, University of São Paulo, Ribeirão Preto, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, UNIFESP/EPM, Brazil; Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Federal University of São Paulo, UNIFESP/EPM, Brazil. Electronic address: vanabilio@gmail.com.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Abílio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage; D048588:Benzoxazines / Q000008:administration & dosage; D063385:Cannabinoid Receptor Modulators / Q000627:therapeutic use*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007398:Interpersonal Relations; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000008:administration & dosage; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000077285:Rimonabant; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C119325:arachidonyl-2-chloroethylamide; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin; C107594:N-(4-hydroxyphenyl)arachidonylamide
keywords: Cannabinoids; Hyperlocomotion; SHR; Schizophrenia; Social interaction; Vanilloid drugs