Effects of cannabidiol on behavioural and gene expression changes
induced by spontaneous cocaine withdrawal
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.