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Blockade of the Cannabinoid CB1 Receptor and Alcohol Dependence: Preclinical Evidence and Preliminary Clinical Data

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The present paper summarizes the results of a number of pharmacological studies implicating the cannabinoid CB1 receptor in the neural circuitry regulating different alcohol-related behaviors in rodents. Specifically, cannabinoid CB1 receptor antagonists - including the prototype, rimonabant - have been reported to suppress: (a) acquisition and maintenance of alcohol drinking behavior under the 2-bottle “alcohol vs water” choice regimen; (b) the increase in alcohol intake occurring after a period of alcohol abstinence (an experimental model of alcohol relapse); (c) alcohol's reinforcing and motivational properties measured in rats trained to perform a specific task (e.g., lever-pressing) to access alcohol; (d) reinstatement of extinguished alcohol-seeking behavior triggered in rats by a nicotine challenge or presentation of cues previously associated to alcohol availability (another model of alcohol relapse). Additional data indicate that the opioid receptor antagonists, naloxone and naltrexone, synergistically potentiate the suppressing effect of rimonabant on alcohol intake and alcohol's motivational properties in rats. Conversely, the two clinical studies conducted to date (one in alcoholdependent individuals and one in nontreatment-seeking heavy alcohol drinkers) yielded less conclusive results. Unfortunately, the recent discontinuation - due to the occurrence of some psychiatric adverse effects - of all trials with cannabinoid CB1 receptor antagonists apparently hinders further investigations on the potential of rimonabant in the treatment of alcohol dependence.

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Keywords: Cannabinoid CB1 receptor antagonists; alcohol; alcohol relapse; animal models of alcoholism; rimonabant

Document Type: Research Article

Publication date: March 1, 2010

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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