High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking
| Autor: | Angela R. Ozburn, Jason P. Schlumbohm, John C. Crabbe, Lawrence C. Huang, Amanda M. Barkley-Levenson, Stephanie E. Spence, Wyatt R. Hack, Pamela Metten |
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| Rok vydání: | 2017 |
| Předmět: |
Agonist
Male Baclofen medicine.drug_class Taurine Acamprosate Clinical Biochemistry Binge drinking Alcohol use disorder Pharmacology Toxicology Biochemistry Naltrexone Article Binge Drinking 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Pharmacotherapy medicine Animals Biological Psychiatry Ethanol Darkness medicine.disease Mice Mutant Strains 030227 psychiatry Mice Inbred C57BL Disease Models Animal chemistry Disulfiram Female Psychology 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacology, biochemistry, and behavior. 160 |
| ISSN: | 1873-5177 |
| Popis: | Background There is a serious public health need for better understanding of alcohol use disorder disease mechanisms and for improved treatments. At this writing, only three drugs are approved by the Food and Drug Administration as medications to treat alcohol use disorders – disulfiram, naltrexone, and acamprosate. Binge drinking is a form of abusive alcohol drinking defined by the NIAAA as a drinking to blood alcohol levels (BALs) > 0.08% during a period of approximately 2 h. To model genetic risk for binge-like drinking, we have used selective breeding to create a unique animal model, High Drinking in the Dark (HDID) mice. Behavioral characterization of HDID mice has revealed that HDID mice exhibit behavioral impairment after drinking, withdrawal after a single binge-drinking session, and escalate their intake in response to induction of successive cycles of dependence. Notably, HDID mice do not exhibit altered tastant preference or alcohol clearance rates. We therefore asked whether drugs of known clinical relevance could modulate binge-like ethanol drinking in HDID mice, reasoning that this characterization of HDID responses should inform future use of this genetic animal model for screening and development of novel potential therapeutics. Methods We tested the efficacy of acamprosate and naltrexone to reduce binge-like drinking in HDID mice. Additionally, we tested the GABA B receptor agonist, baclofen, based on recent pre-clinical and clinical studies demonstrating that it reduces alcohol drinking. We elected not to include disulfiram due to its more limited clinical usage. Mice were tested after acute doses of drugs in the limited-access Drinking in the Dark (DID) paradigm. Results HDID mice were sensitive to the effects of acamprosate and baclofen, but not naltrexone. Both drugs reduced binge-like drinking. However, naltrexone failed to reduce drinking in HDID mice. Thus, HDID mice may represent a useful model for screening novel compounds. |
| Databáze: | OpenAIRE |
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