Kappa-Opioid Receptor Antagonism: A Mechanism for Treatment of Relief Drinking?

  • Markus Heilig
    Address correspondence to Markus Heilig, M.D., Ph.D., NIAAA & NIDA, 10 Center Drive, 10/1E-5334, Bethesda, MD 20892-1108
    Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
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  • Jesse R. Schank
    Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia
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      Of recreational users of alcohol, ~15% at some point go on to develop a pattern of alcohol seeking and taking that continues despite adverse consequences—that is, alcohol addiction or simply alcoholism. This proportion is not much different from what is seen with other drugs of abuse, but more than half of all Americans ≥12 years old report being current drinkers. As a result, in the United States, ~12 million people have a current diagnosis of alcoholism, accounting for a greater disease burden than all illicit drugs combined. Few evidence-based treatments are currently available for these patients. Efficacy of existing treatments is limited further by the heterogeneity of alcoholism. Optimal clinical management of these patients ultimately requires personalized approaches that match treatments to pathophysiologically relevant individual characteristics. Some of these characteristics are clearly genetic, but personalized therapies also need to take in account neuroadaptations that develop over time as a result of alcohol use itself.
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      Linked Article

      • The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors
        Biological PsychiatryVol. 75Issue 10
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          The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations.
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