Antipsychotic Profile of Cannabidiol and Rimonabant in an Animal Model of Emotional Context Processing in Schizophrenia

Raquel      Levin; Valeria      Almeida; Fernanda      Fiel Peres; Mariana      Bendlin Calzavara; Neide      Derci da Silva; Mayra      Akimi Suiama; Suzy      Tamie Niigaki; Antonio      Waldo Zuardi; Jaime      Eduardo Cecilio Hallak; Jose      Alexandre Crippa; Vanessa      Costhek Abilio

doi:10.2174/138161212802884735

Abstract

Objectives: Clinical and neurobiological findings suggest that cannabinoids and their receptors are implicated in schizophrenia. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that spontaneously hypertensive rats (SHR) present a deficit in contextual fear conditioning (CFC) that is specifically ameliorated by antipsychotics and aggravated by proschizophrenia manipulations. These results led us to suggest that the CFC deficit presented by SHR could be used as a model to study emotional processing impairment in schizophrenia. The aim of this study is to evaluate the effects of CBD and rimonabant (CB1 receptor antagonist) on the contextual fear conditioning in SHR and Wistar rats (WR). Methods: Rats were submitted to CFC task after treatment with different doses of CBD (experiment 1) and rimonabant (experiment 2). Results: In experiment 1, SHR showed a decreased freezing response when compared to WR that was attenuated by 1 mg/kg CBD. Moreover, all CBD-treated WR presented a decreased freezing response when compared to control rats. In experiment 2, SHR showed a decreased freezing response when compared to WR that was attenuated by 3 mg/kg rimonabant. Discussion: Our results suggest a potential therapeutical effect of CBD and rimonabant to treat the emotional processing impairment presented in schizophrenia. In addition, our results reinforce the anxiolytic profile of CBD.

Keywords: Schizophrenia, cannabidiol, rimonabant, contextual fear conditioning, SHR, Cannabis sativa, antipsychotics, proschizophrenia, Wistar rats (WR), freezing response.