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Effects of cannabidiol on behavioural and gene expression changes induced by spontaneous cocaine withdrawal
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  • Ani Gasparyan,
  • Francisco Navarrete,
  • Marta Rodriguez-Arias,
  • Jose Miñarro,
  • Jorge Manzanares
Ani Gasparyan
Universidad Miguel Hernandez de Elche - Campus San Juan de Alicante
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Francisco Navarrete
Miguel Hernandez University of Elche - Campus of San Juan de Alicante
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Marta Rodriguez-Arias
University of Valencia
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Jose Miñarro
University of Valencia
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Jorge Manzanares
Universidad Miguel Hernandez de Elche - Campus San Juan de Alicante
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Abstract

Background and purpose. The purpose of this study was to evaluate the effects of CBD on the behavioural and gene expression changes induced by a new animal model of spontaneous cocaine withdrawal. Experimental approach. Six hours after cessation of progressive increase of cocaine administration for 12 days (15 mg·kg-1·day-1 to 60 mg·kg-1·day-1, i.p.), spontaneous cocaine withdrawal was evaluated in male mice. The effects of CBD (10, 20 and 40 mg·kg-1, i.p.) were evaluated on cocaine withdrawal-induced alterations in motor activity, somatic signs and anxiety-like behaviour. Furthermore, gene expression changes in dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the ventral tegmental area, and in cannabinoid receptors 1 (CNR1) and 2 (CNR2) in the nucleus accumbens were analysed by real-time PCR. Key results. Mice exposed to the spontaneous cocaine withdrawal model showed increased motor activity, somatic withdrawal signs and high anxiety-like behaviour. Interestingly, the administration of CBD normalized motor and somatic signs disturbances and induced an anxiolytic effect. Moreover, the administration of CBD blocked the increase of DAT and TH gene expression in mice exposed to the cocaine withdrawal. In addition, the administration of CBD modulated the cocaine withdrawal-induced decrease of CNR1 and induced an additional up-regulation of CNR2 gene expression. Conclusions and implications. These results show behavioural and gene expression alterations in mice exposed to a new model of spontaneous cocaine withdrawal. Interestingly, CBD alleviates cocaine withdrawal-induced behavioural and gene expression alterations suggesting potential for the management of cocaine withdrawal.