Abstract
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.
Highlights
Adolescence is a critical period of accelerated neurodevelopment, which occurs between the ages of approximately 11–21 years in humans and conservative estimates of adolescence in rodents range from postnatal days (PNDs) 28–42 (Spear, 2000, 2010; Laviola et al, 2003)
We have consistently observed decreased immobility in adult drinkers during early withdrawal, which we have interpreted as anxietyrelated hyperactivity in response to an acute stressor (Lee et al, 2015, 2016, 2017). wd1EtOHadults showed increased sucrose preference compared to water control animals, which is not surprising given that studies have shown increased preference
For sweet/sugary drinks amongst both humans (Kampov-Polevoy et al, 1997; Kranzler et al, 2001) and animals (Katz, 1982; Gosnell and Krahn, 1992; Stewart et al, 1994) with a history of chronic alcohol consumption. These results support the presence of hyperanxiety, but not depression, in wd1EtOHadults. These alcohol-induced behavioral differences dissipated during the course of withdrawal and by day 28, wd28EtOHadults showed no significant differences compared to PND98 water control animals
Summary
Adolescence is a critical period of accelerated neurodevelopment, which occurs between the ages of approximately 11–21 years in humans and conservative estimates of adolescence in rodents range from postnatal days (PNDs) 28–42 (Spear, 2000, 2010; Laviola et al, 2003). There is a dramatic reduction of gray matter as the cortex undergoes synaptic pruning, and a proliferation of white matter from ongoing myelination of axons, leading to extensive remodeling of the structure and function of the brain (e.g., Sowell et al, 2003; Gogtay et al, 2004). These processes are essential for refining excitatory and inhibitory connectivity and stabilizing synapses within corticofugal projections that exert control over subcortical hyperactivation (Casey et al, 2011; Sturman and Moghaddam, 2011; Arain et al, 2013). Research has consistently shown that adolescent drinking is one of the strongest predictors of substance abuse problems and addiction later in life (Grant and Dawson, 1997; Chassin et al, 2002; Tapert and Schweinsburg, 2005)
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