Escalating ethanol intake is associated with altered corticostriatal BDNF expression.
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.
Logrip
Marian L
ML
The Gallo Research Center, University of California, San Francisco, Emeryville, California 94608, USA.
Janak
Patricia H
PH
Ron
Dorit
D
D000428:Alcohol Drinking / Q000473:pathology* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002755:Choice Behavior / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D005518:Food Preferences / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012646:Self Administration
D019208:Brain-Derived Neurotrophic Factor