A novel mouse model for vulnerability to alcohol dependence induced by early-life adversity
| العنوان: | A novel mouse model for vulnerability to alcohol dependence induced by early-life adversity |
|---|---|
| المؤلفون: | Candice Contet, Agbonlahor Okhuarobo, Eric P. Zorrilla, Jessica L. Bolton, Tallie Z. Baram, Ighodaro Igbe |
| المصدر: | Neurobiology of Stress Neurobiology of Stress, Vol 13, Iss, Pp 100269-(2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Physiology, Alcohol, Cardiovascular, Biochemistry, Oral and gastrointestinal, lcsh:RC346-429, Substance Misuse, Alcohol Use and Health, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Corticosterone, 2.1 Biological and endogenous factors, Medicine, Original Research Article, Aetiology, media_common, lcsh:QP351-495, Alcoholism, Coping, Elevated plus maze, media_common.quotation_subject, Addiction, Affect (psychology), Basic Behavioral and Social Science, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Behavioral and Social Science, Early-life stress, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, Ethanol, Resilience, Endocrine and Autonomic Systems, business.industry, Alcohol dependence, Neurosciences, Tail suspension test, Brain Disorders, 030227 psychiatry, Good Health and Well Being, lcsh:Neurophysiology and neuropsychology, chemistry, business, Negative reinforcement, 030217 neurology & neurosurgery |
| الوصف: | Childhood adversity increases vulnerability to alcohol use disorders and preclinical models are needed to investigate the underlying neurobiological mechanisms. The present study modeled early-life adversity by rearing male and female C57BL/6J mouse pups in a limited bedding and nesting (LBN) environment, which induces erratic maternal care. As adults, mice were given limited access to two-bottle choice (2BC) alcohol drinking, combined or not with chronic intermittent ethanol (CIE) vapor inhalation to induce alcohol dependence. We tested the hypothesis that LBN rearing might exacerbate or facilitate the emergence of the motivational and affective effects of CIE. Consistent with our hypothesis, although LBN-reared males consumed the same baseline levels of alcohol as controls, they escalated their ethanol intake at an earlier stage of CIE exposure, i.e., after 4 rounds vs. 5 rounds for controls. In contrast, females were insensitive to both LBN rearing and CIE exposure. Males were further subjected to a behavioral test battery. Withdrawal from CIE-2BC increased digging activity and lowered mechanical nociceptive thresholds regardless of early-life conditions. On the other hand, LBN-reared CIE-2BC males showed reduced open arm exploration in the elevated plus maze and increased immobility in the tail suspension test compared to alcohol-naïve counterparts, while no group differences were detected among control-reared males. Finally, LBN rearing and alcohol exposure did not affect grooming in response to a sucrose spray (splash test), novel object recognition, or corticosterone levels. In summary, the LBN experience accelerates the transition from moderate to excessive alcohol drinking and produces additional indices of affective dysfunction during alcohol withdrawal in C57BL/6J male mice. Highlights • Early-life adversity was generated by rearing C57BL/6J mouse pups in a limited bedding and nesting (LBN) environment. • Alcohol dependence was induced in adulthood via chronic intermittent ethanol (CIE) inhalation. • The LBN experience accelerated alcohol intake escalation in males. • LBN exacerbated affective disturbances upon CIE withdrawal in males. • Alcohol intake in females was insensitive to both LBN and CIE. |
| وصف الملف: | application/pdf |
| تدمد: | 2352-2895 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74b2ffdb86ea88a6048df52830bfd3e0 https://doi.org/10.1016/j.ynstr.2020.100269 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....74b2ffdb86ea88a6048df52830bfd3e0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23522895 |
|---|