An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice
| Autor: | Lawrence C. Huang, John C. Crabbe, Jason P. Schlumbohm, Gian D. Greenberg, Wyatt R. Hack, Pamela Metten, Stephanie E. Spence |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Health (social science) Individuality Physiology Alcohol Physical dependence Anxiety Motor Activity Toxicology Biochemistry Article Developmental psychology Alcohol Withdrawal Seizures 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Inbred strain Species Specificity Administration Inhalation medicine Animals Pain Measurement Behavior Animal Ethanol Genetic heterogeneity Depression Alcohol dependence Anhedonia Central Nervous System Depressants General Medicine Hypothermia medicine.disease Substance Withdrawal Syndrome 030104 developmental biology Neurology chemistry Alcohol withdrawal syndrome Ataxia Female medicine.symptom Psychology 030217 neurology & neurosurgery |
| Zdroj: | Alcohol (Fayetteville, N.Y.). 68 |
| ISSN: | 1873-6823 |
| Popis: | Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes. |
| Databáze: | OpenAIRE |
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