The Effects of Severe Psychological Stress Coupled with Binge Drinking on Markers of Skeletal Muscle Protein Synthesis

Abstract

Acute exposure to a severe stressor can cause an increase in circulating glucocorticoid (GC) concentrations by approximately ten-fold, which can remain elevated for as long as ten days. Elevated GCs can promote skeletal muscle atrophy and diminish muscle strength. Unfortunately, a common coping mechanism in response to severe stress is the use and abuse of alcohol. Alcohol abuse also suppresses muscle protein synthesis; thus, the combination of stress and alcohol may exacerbate skeletal muscle impairments. The aim of this current study was to examine the combined effects of stress and alcohol on muscle protein synthesis signaling in skeletal muscle. Our hypothesis was that voluntary binge-patterned drinking preceded by acute stress would impair signaling of muscle protein synthesis compared to binge drinking alone. Male C57BL/6 mice (7 weeks old) were exposed to a single episode of 100 inescapable tail shocks. Following acute stress, mice were randomized into groups with temporary access to either water or alcohol during their active period daily for 5 days, a voluntary binge-patterned drinking protocol referred to as Drinking in the Dark (DID). On the fifth day, following DID, mice were euthanized, and muscles of interest were rapidly collected. The experimental set up resulted in 2 groups: Stress Alcohol (SA) (n=7) and Stress Water (SW) (n=8). Gastrocnemius was analyzed via western blotting and the canonical Akt-mTORC1 pathway of protein synthesis was assessed for changes in signaling. The SA group tended to have less phosphorylation of Akt (p=0.068), but there was no difference in the phosphorylation of mTOR between groups (p=0.838). The SA group tended to have less phosphorylation of p70S6 kinase (p=0.058), a downstream target of mTORC1. Similarly, phosphorylation of 4E Binding Protein 1 (p4EBP1) was significantly lower in SA (p=0.017). Our results suggest binge drinking in the context of stress may impair muscle protein synthesis along the Akt-mTORC1 pathway.