期刊
JOURNAL OF NEUROCHEMISTRY
卷 109, 期 5, 页码 1459-1468出版社
WILEY
DOI: 10.1111/j.1471-4159.2009.06073.x
关键词
addiction; alcohol; cortex; dorsal striatum; neurotrophic factor
资金
- NIAAA [RO1 AA016848, F31 AA015462]
- State of California for Medical Research on Alcohol and Substance Abuse through the University of California, San Francisco
- NIAAA award [U01 AA013489]
- Department of the Army [W81XWH-05-1-0212]
Alcoholism is a chronically relapsing condition, indicative of long-term neuronal adaptations maintaining the disease even after prolonged abstinence. Previously, we identified brain-derived neurotrophic factor (BDNF) in the dorsal striatum as the central mediator of a homeostatic mechanism which is activated by acute alcohol (ethanol) exposure and functions to decrease the sensitivity of rodents to ethanol-related behaviors. We hypothesized that extensive exposure to ethanol would result in dysregulation of this BDNF-mediated protective mechanism, accompanied by heightened ethanol intake. In this study, we demonstrate that while a single bout of ethanol intake increases BDNF mRNA expression in the dorsal striatum, this effect is no longer observed after 6 weeks of daily ethanol access. Additionally, 6 weeks of ethanol consumption decreases BDNF in the cortex, a main source of BDNF for the striatum. Importantly, these ethanol-induced changes in BDNF levels are not ameliorated by 2 weeks' abstinence. Together, these data suggest that the BDNF pathway, which is activated following a single bout of ethanol drinking, breaks down by the end of 6 weeks of access and does not recover its protective function after a 2-week deprivation period. These results suggest that the persistence of altered BDNF signaling may contribute to the inflexibility of addictive behaviors.
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