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

Autor(es)

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

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Pharmacol, BR-04039032 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 Sao Paulo - Brazil

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

^[4] Natl Council Sci & Technol Dev, Natl Inst Sci & Technol Translat Med, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 5, FEB 6 2014.
• Citações Web of Science: 36

Resumo

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. (AU)

• Processo FAPESP: 10/07994-3 - Participação das transmissões dopaminérgica e endocanabinóide em um modelo animal de esquizofrenia: a linhagem SHR
• Beneficiário: Vanessa Costhek Abílio
• Modalidade de apoio: Auxílio à Pesquisa - Regular