Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
E DomiMarkus Heilig

Abstract

Prior work suggests a role of kappa-opioid signaling in the control of alcohol drinking, in particular when drinking is escalated due to alcohol-induced long-term neuroadaptations. Here, we examined the small molecule selective kappa antagonist CERC-501 in rat models of alcohol-related behaviors, with the objective to evaluate its potential as a candidate therapeutic for alcohol use disorders. We first tested the effect of CERC-501 on acute alcohol withdrawal-induced anxiety-like behavior. CERC-501 was then tested on basal as well as escalated alcohol self-administration induced by 20% alcohol intermittent access. Finally, we determined the effects of CERC-501 on relapse to alcohol seeking triggered by both stress and alcohol-associated cues. Control experiments were performed to confirm the specificity of CERC-501 effects on alcohol-related behaviors. CERC-501 reversed anxiety-like behavior induced by alcohol withdrawal. It did not affect basal alcohol self-administration but did dose-dependently suppress self-administration that had escalated following long-term intermittent access to alcohol. CERC-501 blocked relapse to alcohol seeking induced by stress, but not when relapse-like behavior was triggered by alcohol-associated ...Continue Reading

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R SpanagelT S Shippenberg
Jan 1, 1984·Annual Review of Neuroscience·H AkilJ M Walker
Jul 23, 1999·Annals of the New York Academy of Sciences·Y L HurdM Pontén
Oct 7, 2004·European Journal of Pharmacology·Ivy CarrollLouis S Harris
May 18, 2005·Alcoholism, Clinical and Experimental Research·Krisztina M KovacsCsaba Vadasz
Nov 5, 2005·Alcoholism, Clinical and Experimental Research·Peter W MarinelliChristina Gianoulakis
Aug 10, 2006·Journal of Neural Transmission·T HillemacherS Bleich
May 3, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Brendan M Walker, George F Koob
Jun 26, 2008·Psychopharmacology·Van A Redila, Charles Chavkin
Aug 2, 2008·Alcoholism, Clinical and Experimental Research·Jeffrey A SimmsSelena E Bartlett
Sep 29, 2009·Brain Research·Allison T Knoll, William A Carlezon
Feb 13, 2010·Addiction Biology·Markus HeiligHoward C Becker
Nov 3, 2010·Alcoholism, Clinical and Experimental Research·Sebastien CarnicellaDorit Ron
Dec 3, 2010·Alcoholism, Clinical and Experimental Research·Julia WilhelmThomas Hillemacher
Jun 20, 2012·Trends in Neurosciences·Eduardo R ButelmanMary Jeanne Kreek
Sep 22, 2012·Addiction Biology·Ildikó RáczAndreas Zimmer
Dec 6, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anthony L BergerBrendan M Walker
Apr 25, 2013·Biological Psychiatry·Jessica L KisslerBrendan M Walker
May 2, 2014·Biological Psychiatry·Markus Heilig, Jesse R Schank
May 13, 2014·The Journal of Pharmacology and Experimental Therapeutics·John R Cashman, Marc R Azar
Nov 19, 2014·Addiction Biology·Marcus W Meinhardt, Wolfgang H Sommer
Jan 17, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Nicole A Crowley, Thomas L Kash
Jan 30, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeffrey J BudaBradford B Walters
Apr 17, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cody A SicilianoSara R Jones
May 15, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hugo A TejedaPatricio O'Donnell
Dec 3, 2015·The Journal of Pharmacology and Experimental Therapeutics·Mika NaganawaRichard E Carson
Oct 5, 2016·Depression and Anxiety·William A Carlezon, Andrew D Krystal

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Citations

Sep 28, 2018·PloS One·Jordan D LewickyHoang-Thanh Le
Apr 13, 2019·The Journal of Pharmacology and Experimental Therapeutics·Eduardo R ButelmanMary Jeanne Kreek
May 13, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Charles Chavkin
Dec 18, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Rachel I AndersonHoward C Becker
Jan 23, 2021·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Ana DomiEsi Domi
Jun 24, 2020·Peptides·Richard J Bodnar
Mar 12, 2021·Journal of Neurochemistry·Esi DomiEric Augier
Jun 28, 2018·Neuroscience and Biobehavioral Reviews·Shannyn G GendersElvan Djouma
Feb 2, 2019·Journal of Medicinal Chemistry·Miguel GuerreroEdward Roberts

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