Alcohol use across the lifespan: An analysis of adolescent and aged rodents and humans

Novier, Adelle; Diaz-Granados, Jaime L.; Matthews, Douglas B.

doi:10.1016/j.pbb.2015.03.015

Cited by 56 publications

(34 citation statements)

References 290 publications

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“…In both humans and animal models, adolescents typically consume larger quantities of alcohol than adults per drinking episode and adolescents also respond differently to alcohol than their adult counterparts (White et al, 2002; Spear and Varlinskaya, 2005; Novier et al, 2015). Adult drinkers often show pronounced signs of acute withdrawal following a binge episode, including headaches, anxiety, agitation, lethargy, gastrointestinal distress, in severe cases even withdrawal-induced seizures (Knapp et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Negative Affect and Excessive Alcohol Intake Incubate during Protracted Withdrawal from Binge-Drinking in Adolescent, But Not Adult, Mice

et al. 2017

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Binge-drinking is common in underage alcohol users, yet we know little regarding the biopsychological impact of binge-drinking during early periods of development. Prior work indicated that adolescent male C57BL6/J mice with a 2-week history of binge-drinking (PND28-41) are resilient to the anxiogenic effects of early alcohol withdrawal. Herein, we employed a comparable Drinking-in-the-Dark model to determine how a prior history of binge-drinking during adolescence (EtOHadolescents) influences emotionality (assayed with the light-dark box, marble burying test, and the forced swim test) and the propensity to consume alcohol in later life, compared to animals without prior drinking experience. For additional comparison, adult mice (EtOHadults) with comparable drinking history (PND56-69) were subdivided into groups tested for anxiety/drinking either on PND70 (24 h withdrawal) or PND98 (28 days withdrawal). Tissue from the nucleus accumbens shell (AcbSh) and central nucleus of the amygdala (CeA) was examined by immunoblotting for changes in the expression of glutamate-related proteins. EtOHadults exhibited some signs of hyperanxiety during early withdrawal (PND70), but not during protracted withdrawal (PND98). In contrast, EtOHadolescents exhibited robust signs of anxiety-l and depressive-like behaviors when tested as adults on PND70. While all alcohol-experienced animals subsequently consumed more alcohol than mice drinking for the first time, alcohol intake was greatest in EtOHadolescents. Independent of drinking age, the manifestation of withdrawal-induced hyperanxiety was accompanied by reduced Homer2b expression within the CeA and increased Group1 mGlu receptor expression within the AcbSh. The present data provide novel evidence that binge-drinking during adolescence produces a state characterized by profound negative affect and excessive alcohol consumption that incubates with the passage of time in withdrawal. These data extend our prior studies on the effects of subchronic binge-drinking during adulthood by demonstrating that the increase in alcoholism-related behaviors and glutamate-related proteins observed in early withdrawal dissipate with the passage of time. Our results to date highlight a critical interaction between the age of binge-drinking onset and the duration of alcohol withdrawal in glutamate-related neuroplasticity within the extended amygdala of relevance to the etiology of psychopathology, including pathological drinking, in later life.

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Section: Introductionmentioning

confidence: 99%

Negative Affect and Excessive Alcohol Intake Incubate during Protracted Withdrawal from Binge-Drinking in Adolescent, But Not Adult, Mice

et al. 2017

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“…During this transition from childhood to adulthood, adolescents show distinct behavioral and psychological differences, compared to adults (Dahl, 2004). For instance, adolescents show less positive responses to stimuli of low or moderate incentive value, which is thought to drive adolescents to seek-out stronger reinforcement by engaging in impulsive, risky behaviors such as drug use (Novier et al, 2015). Additionally, adolescents have higher basal levels of anxiety and depression and are more vulnerable to stress (Spear, 2002), which may be a source of negative reinforcement that encourages drug use.…”

Section: Introductionmentioning

confidence: 99%

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

Lee

Coelho

McGregor

et al. 2016

Front. Cell. Neurosci.

124

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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.

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“…Older individuals are more sensitive to alcohol, alcohol-induced motor impairments and cognitive deficits (Heuberger, 2009, Novier et al, 2015). Surprisingly, little is known about endogenous factors influencing alcohol toxicity during middle and old age.…”

Section: Introductionmentioning

confidence: 99%

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

Nobrega

Mellers

Lyons

2017

Experimental Gerontology

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Alcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens. Decreased circadian modulation is correlated with significantly greater alcohol sensitivity during the subjective day. The circadian clock modulates alcohol-induced mortality in younger flies with increased mortality following alcohol exposure at night. Older flies exhibit significantly longer recovery times following alcohol-induced sedation and increased mortality following binge-like or chronic alcohol exposure. Flies rendered arrhythmic either genetically or environmentally exhibit significantly increased alcohol sensitivity, longer recovery times and increased mortality. We hypothesize that the circadian clock phase specifically buffers behavioral and cellular alcohol sensitivity with this protection diminishing as the circadian clock weakens with age.

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Alcohol use across the lifespan: An analysis of adolescent and aged rodents and humans

Cited by 56 publications

References 290 publications

Negative Affect and Excessive Alcohol Intake Incubate during Protracted Withdrawal from Binge-Drinking in Adolescent, But Not Adult, Mice

Negative Affect and Excessive Alcohol Intake Incubate during Protracted Withdrawal from Binge-Drinking in Adolescent, But Not Adult, Mice

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

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