Changes in endocannabinoid contents in reward-related brain regions of alcohol-exposed rats, and their possible relevance to alcohol relapse

Authors

  • Sara González,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain
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  • Marta Valenti,

    1. Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, 80078-Pozzuoli, Napoli, Italy
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  • Rosario de Miguel,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain
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  • Filomena Fezza,

    1. Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, 80078-Pozzuoli, Napoli, Italy
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  • Javier Fernández-Ruiz,

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain
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  • Vincenzo Di Marzo,

    Corresponding author
    1. Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, 80078-Pozzuoli, Napoli, Italy
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  • José A Ramos

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain
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Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain. E-mail: jjfr@med.ucm.es

Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, 80078-Pozzuoli, Napoli, Italy. E-mail: vdimarzo@icmib.na.cnr.it

Abstract

  • Chronic alcohol exposure modifies endocannabinoid levels in different brain regions, while pharmacological targeting of the endocannabinoid system has been reported to influence ethanol intake in laboratory animals.

  • The present study was aimed at evaluating the pattern of changes of endocannabinoids and their receptors, with emphasis on reward-related brain areas, in Wistar rats subjected to consecutive phases of alcoholization, alcohol deprivation (abstinence), and voluntary consumption of alcohol (relapse).

  • We observed that, in the limbic forebrain, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) contents increased after 7 days of alcoholization, then to dramatically decrease after 48 h of alcohol deprivation and, in the case of 2-AG, to further decrease when rats were allowed to relapse to alcohol consumption. By contrast, in the midbrain, there was a marked reduction in AEA, but not 2-AG, content, after alcoholization. This decrease was not affected during alcohol abstinence, but both AEA and 2-AG contents were then significantly reduced when rats were allowed to relapse to alcohol consumption.

  • Based on these data, we examined whether pharmacological activation/blockade of endocannabinoid transmission might influence ethanol intake in rats allowed to relapse to alcohol consumption after subsequent periods of alcoholization and alcohol deprivation.

  • Treatment with either Δ9-tetrahydrocannabinol or CP55,940, two cannabinoid agonists, reduced both total liquid and ethanol intake but did not affect ethanol preference. Treatment with SR141716, a selective cannabinoid CB1 receptor antagonist, also produced a significant reduction in both total liquid and ethanol intake without affecting ethanol preference. Accordingly, none of these effects on ethanol intake were accompanied by changes in dopamine and GABA in limbic structures.

  • In summary, the levels of endocannabinoids underwent significant changes in reward-related areas during alcoholization, alcohol deprivation, and relapse, showing the lowest values in this latter phase. Treatment with cannabinoid agonists or a selective CB1 receptor antagonist resulted in a reduction of ethanol intake by rats allowed to relapse to alcohol consumption after periods of alcoholization and alcohol deprivation, but these effects did not appear to be due to changes in neurobiological substrates currently involved in alcohol reinforcement/relapse.

British Journal of Pharmacology (2004) 143, 455–464. doi:10.1038/sj.bjp.0705963

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