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Open Access | 10.1172/JCI159103
1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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Light, J.
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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Roberto, M.
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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1Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, United States of America
2Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, United States of America
3Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, United States of America
4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, United States of America
5Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States of America
6Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, United States of America
7Psychology, Oregon Research Institute, Portland, United States of America
8Oregon Health & Science University (OHSU), Portland, United States of America
9Department of Neuroscience, Medical University of South Carolina, Charleston, United States of America
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Published January 19, 2023 - More info
Treatment options for Alcohol Use Disorders (AUD) have minimally advanced since 2004, while the annual deaths and economic toll have increased alarmingly. Phosphodiesterase type 4 (PDE4) is associated with alcohol and nicotine dependence. PDE4 inhibitors were identified as a potential AUD treatment using a novel bioinformatics approach. We prioritized a newer PDE4 inhibitor, apremilast, as ideal for repurposing, (i.e. FDA approved for psoriasis, low incidence of adverse events, excellent safety profile), and tested it using multiple animal strains and models, as well as in a human Phase IIa study. We found that apremilast reduced binge-like alcohol intake and behavioral measures of alcohol motivation in mouse models of genetic risk for drinking to intoxication. Apremilast also reduced excessive alcohol drinking in models for stress-facilitated drinking and alcohol dependence. Using site-directed drug infusions and electrophysiology, we uncovered that apremilast may act to lessen drinking in mice by increasing neural activity in the nucleus accumbens, a key brain region in the regulation of alcohol intake. Importantly, apremilast (90 mg/d) reduced excessive drinking in non-treatment seeking individuals with AUD in a double blind, placebo-controlled study. These results demonstrate that apremilast suppresses excessive alcohol drinking across the spectrum of AUD severity.