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Levin R, Peres FF, Almeida V, et al. Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Front Pharmacol. 2014;5:10doi: 10.3389/fphar.2014.00010.
Levin, R., Peres, F. F., Almeida, V., Calzavara, M. B., Zuardi, A. W., Hallak, J. E., Crippa, J. A., & Abílio, V. C. (2014). Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Frontiers in pharmacology, 510. https://doi.org/10.3389/fphar.2014.00010
Levin, Raquel, et al. "Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain." Frontiers in pharmacology vol. 5 (2014): 10. doi: https://doi.org/10.3389/fphar.2014.00010
Levin R, Peres FF, Almeida V, Calzavara MB, Zuardi AW, Hallak JE, Crippa JA, Abílio VC. Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Front Pharmacol. 2014 Feb 06;5:10. doi: 10.3389/fphar.2014.00010. eCollection 2014. PMID: 24567721; PMCID: PMC3915876.
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Front Pharmacol. 2014 Feb 06;5:10. doi: 10.3389/fphar.2014.00010. eCollection 2014.

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

Frontiers in pharmacology

Raquel Levin, Fernanda F Peres, Valéria Almeida, Mariana B Calzavara, Antonio W Zuardi, Jaime E C Hallak, José Alexandre S Crippa, Vanessa C Abílio

Affiliations

  1. 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.
  2. Laboratório Interdisciplinar de Neurociãncias Clínicas, Department of Psychiatry, Federal University of São Paulo São Paulo, Brazil.
  3. 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.

PMID: 24567721 PMCID: PMC3915876 DOI: 10.3389/fphar.2014.00010

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.

Keywords: PPI; SHR; animal model; cannabinoid drugs; schizophrenia

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