Cannabidiol effects on cocaine-seeking behaviour and incubation of craving in mice

Abstract

ABSTRACT Background and Purpose To remain abstinent represents one of the major challenges for the treatment of cocaine use disorder. Cocaine seeking elicited by drug-associated cues progressively intensifies during abstinence in a process termed incubation of craving, representing an aggravating factor for relapse. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-seeking behaviour, although its effects on cocaine-craving incubation have never been elucidated. Experimental Approach We developed a mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. Changes in the protein expression of AMPAR subunits and ERK 1/2 phosphorylation were analysed. We also assessed the effects of cannabidiol (20 mg·kg -1 ) administered either during acquisition of cocaine self-administration or abstinence. Key Results Mice efficiently performed the demand task and incubation of cocaine craving. Besides, changes in GluA1 and GluA2 protein levels were found along the abstinence in prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK 1/2 phosphorylation in ventral striatum. Cannabidiol reduced ongoing cocaine intake when administered during the acquisition phase of the self-administration, but failed to alter the subsequent demand task performance and incubation of cocaine craving. No effects were found when cannabidiol was administered during the abstinence period. Conclusion and Implications We provide here a novel model of behavioural economic analysis of demand curves and cue-induced incubation of cocaine-seeking behaviour for mice. Moreover, we show that cannabidiol exerts differential effects on the current model depending on the self-administration phase in which it was administered. What is already known Behavioural economics and incubation of cocaine craving are well-stablished paradigms to evaluate cocaine seeking in rats. CBD reduces cocaine-seeking and cocaine-taking behaviours. What this study adds A mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. CBD reduces cocaine self-administration and has no effect over demand task and cocaine-craving incubation. Clinical significance A new behavioural model for studying cocaine addiction in mice. CBD exerts differential effects depending on when it was administered in the addictive process. T ables of L inks