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

Abstract

Background and PurposeTo 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 ApproachWe 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 ERK1/2 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 ResultsMice 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 ERK1/2 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 ImplicationsWe 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 knownBehavioural 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 addsA 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 significanceA new behavioural model for studying cocaine addiction in mice.CBD exerts differential effects depending on when it was administered in the addictive process.Tables of Links

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

“…Regarding addiction, previous literature has pointed out the protective role of CBD for the treatment of psychostimulants abuse (Calpe-López et al, 2019;Rodrigues et al, 2020). Our team reported that CBD (20 mg/kg) decreased cocaine-induced acquisition of CPP in mice (Luján et al, 2018) and cocainemaintained self-administration (Alegre-Zurano et al, 2020a;Luján et al, 2019Luján et al, , 2018, as well as cocaine-induced drug-seeking behaviour (Luján et al, 2018). Similarly, Parker et al (2004) found that CBD potentiated the extinction of both cocaine-induced and amphetamine-induced CPP in rats and methamphetamine-induced drug-seeking behaviour (Hay et al, 2018).…”

“…The surgical procedure was conducted as previously described (Alegre-Zurano et al, 2020a;Soria et al, 2005). Surgical implantation of the catheter into the jugular vein was performed following anaesthetization with a mixture of ketamine hydrochloride (75 mg•kg -1 ; Imalgène1000, Lyon, France) and medetomidine hydrochloride (1 mg•kg -1 ; Medeson®, Barcelona, Spain).…”

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

“…The surgical procedure was conducted as previously described [ 35 , 39 ]. Surgical implantation of the catheter into the jugular vein was performed following anaesthetisation with a mixture of ketamine hydrochloride (75 mg·kg −1 ; Imalgène1000, Lyon, France) and medetomidine hydrochloride (1 mg·kg −1 ; Medeson ® , Barcelona, Spain).…”

“…Regarding addiction, the existing literature has pointed out the protective role of CBD for treating psychostimulants abuse [ 31 , 32 ]. Our team reported that CBD (20 mg/kg) decreased cocaine-induced acquisition of CPP in mice [ 33 ] and cocaine-maintained self-administration [ 33 , 34 , 35 ], as well as cocaine-induced drug-seeking behaviour [ 33 ]. Similarly, CBD potentiated the extinction of cocaine-induced and amphetamine-induced CPP in rats [ 36 ] and methamphetamine-induced drug-seeking behaviour [ 37 ].…”