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

ABSTRACTBackground 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

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Dehydroepiandrosterone (DHEA) attenuates cocaine-seeking behavior in the self-administration model in rats

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2005.10.002 ◽

2006 ◽

Vol 16 (5) ◽

pp. 329-339 ◽

Cited By ~ 20

Author(s):

Rachel Maayan ◽

Sharon Lotan ◽

Ravid Doron ◽

Maytal Shabat-Simon ◽

Iris Gispan-Herman ◽

...

Keyword(s):

The Self ◽

Self Administration ◽

Cocaine Seeking ◽

Seeking Behavior

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A95 DHEA ATTENUATES COCAINE-SEEKING BEHAVIOR IN THE SELF-ADMINISTRATION MODEL IN RATS

Behavioural Pharmacology ◽

10.1097/00008877-200509001-00168 ◽

2005 ◽

Vol 16 (Supplement 1) ◽

pp. S53

Author(s):

R. Maayan ◽

S. Lotan ◽

A. Weizman ◽

G. Yadid

Keyword(s):

The Self ◽

Self Administration ◽

Cocaine Seeking ◽

Seeking Behavior

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Impulsivity and Drug Addiction: A Neurobiological Perspective

10.1093/oxfordhb/9780195389715.013.0078 ◽

2012 ◽

Author(s):

Trevor Robbins

Keyword(s):

Drug Addiction ◽

Conceptual Analysis ◽

Animal Studies ◽

Reaction Time Task ◽

Compulsive Behavior ◽

Self Administration ◽

Detailed Characterization ◽

Cocaine Seeking ◽

Serial Reaction

A conceptual analysis of the impulsivity construct in behavioral and neurobiological terms is followed by an analysis of its causal role in certain forms of drug addiction in both human and animal studies. The main focus of this chapter is on a rat model of impulsivity based on premature responding in the five-choice serial reaction time task and a more detailed characterization of this phenotype in neurobehavioral, neurochemical, and genetic terms. Evidence is surveyed that high impulsivity on this task is associated with the escalation subsequently of cocaine self-administration behavior and also with a tendency toward compulsive cocaine seeking. Novelty reactivity, by contrast, is associated with the enhanced acquisition of self-administration, but not with the escalation of intravenous self-administration of cocaine or the development of compulsive behavior associated with cocaine seeking. These results indicate that the vulnerability to stimulant addiction may depend on different factors, as expressed through distinct presumed endophenotypes. These observations help us further to dissociate various aspects of the impulsivity construct in neural as well as behavioral terms.

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History and Personal Autonomy

Canadian Journal of Philosophy ◽

10.1080/00455091.1993.10717320 ◽

1993 ◽

Vol 23 (2) ◽

pp. 271-280 ◽

Cited By ~ 9

Author(s):

Alfred Mele

Keyword(s):

Personal Autonomy ◽

The Self ◽

Personal History ◽

Individual Autonomy ◽

List Type ◽

Historical Account ◽

New Model ◽

Self Reflection

John Christman, in ‘Autonomy and Personal History,’ advances a novel genetic or historical account of individual autonomy. He formulates ‘the conditions of the [i.e., his] new model of autonomy’ as follows:(i) A person P is autonomous relative to some desire D if it is the case that P did not resist the development of D when attending to this process of development, or P would not have resisted that development had P attended to the process;(ii) The lack of resistance to the development of D did not take place (or would not have) under the influence of factors that inhibit self-reflection;and(iii) The self-reflection involved in condition (i) [sic] is (minimally) rational and involves no self-deception. (11)

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Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants.

Psychological Review ◽

10.1037/0033-295x.91.2.251 ◽

1984 ◽

Vol 91 (2) ◽

pp. 251-268 ◽

Cited By ~ 774

Author(s):

Jane Stewart ◽

Harriet de Wit ◽

Roelof Eikelboom

Keyword(s):

Drug Effects ◽

The Self ◽

Self Administration

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Antonios Karampatzos: Private Law, Nudging and Behavioural Economic Analysis – The Mandated-Choice Model, London und New York: Routledge 2020. 174 S.; 143,50 €. ISBN 978–0-367–41032–2.

Archiv für die civilistische Praxis ◽

10.1628/acp-2021-0009 ◽

2021 ◽

Vol 221 (1-2) ◽

pp. 259

Keyword(s):

New York ◽

Economic Analysis ◽

Choice Model ◽

Private Law ◽

Behavioural Economic

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Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

Journal of Psychopharmacology ◽

10.1177/0269881118812098 ◽

2018 ◽

Vol 33 (1) ◽

pp. 132-144

Author(s):

Tracey A Larson ◽

Casey E O’Neill ◽

Michaela P Palumbo ◽

Ryan K Bachtell

Keyword(s):

Dose Response ◽

Extinction Training ◽

Schedules Of Reinforcement ◽

Sprague Dawley ◽

Self Administration ◽

Caffeine Consumption ◽

Adult Rats ◽

Sprague Dawley Rats ◽

Cocaine Seeking ◽

Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

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Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

10.1101/385039 ◽

2018 ◽

Author(s):

Julie Corre ◽

Ruud van Zessen ◽

Michaël Loureiro ◽

Tommaso Patriarchi ◽

Lin Tian ◽

...

Keyword(s):

Nucleus Accumbens ◽

Causal Link ◽

The Self ◽

Dopamine Neurons ◽

Self Administration ◽

Gaba Neurons ◽

Calcium Indicators ◽

Compulsive Consumption ◽

Self Stimulation ◽

Stimulation Of

AbstractThe dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we use genetically encoded DA and calcium indicators as well as cFos to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.

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