Kaziya M. Lee, Michal A. Coelho, Hadley A. McGregor, Noah R. Solton, Matan Cohen, Karen K. Szumlinski
Abstract
Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence). Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v) for 2 h/day), while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh) and core (AcbC) subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations (BACs); however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test (FST) compared to water drinkers, which was paralleled by an increase in AcbC levels of GluN2b. Thus, a 2-week period of binge-drinking is sufficient to produce a hyper-anxious state and related increases in protein indices of Acb glutamate function. In contrast, adolescents were resilient to many of the effects of early alcohol withdrawal and this attenuated sensitivity to the negative consequences of binge drinking may facilitate greater alcohol intake in adolescent drinkers.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 December 2016.
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#6,822,151
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Outputs from Frontiers in Cellular Neuroscience
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Outputs of similar age from Frontiers in Cellular Neuroscience
#14
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Altmetric has tracked 22,901,818 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 4,258 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has gotten more attention than average, scoring higher than 70% of its peers.
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We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
