Dataset Information

The Influence of Moderate Physical Activity on Brain Monoaminergic Responses to Binge-Patterned Alcohol Ingestion in Female Mice.

ABSTRACT: Monoamine neurotransmitter activity in brain reward, limbic, and motor areas play key roles in the motivation to misuse alcohol and can become modified by exercise in a manner that may affect alcohol craving. This study investigated the influence of daily moderate physical activity on monoamine-related neurochemical concentrations across the mouse brain in response to high volume ethanol ingestion. Adult female C57BL/6J mice were housed with or without 2.5 h of daily access to running wheels for 30 days. On the last 5 days, mice participated in the voluntary binge-like ethanol drinking procedure, "Drinking in the dark" (DID). Mice were sampled immediately following the final episode of DID. Monoamine-related neurochemical concentrations were measured across brain regions comprising reward, limbic, and motor circuits using ultra High-Performance Liquid Chromatography (UHPLC). The results suggest that physical activity status did not influence ethanol ingestion during DID. Moreover, daily running wheel access only mildly influenced alcohol-related norepinephrine concentrations in the hypothalamus and prefrontal cortex, as well as serotonin turnover in the hippocampus. However, access to alcohol during DID eliminated wheel running-related decreases of norepinephrine, serotonin, and 5-HIAA content in the hypothalamus, but also to a lesser extent for norepinephrine in the hippocampus and caudal cortical areas. Finally, alcohol access increased serotonin and dopamine-related neurochemical turnover in the striatum and brainstem areas, regardless of physical activity status. Together, these data provide a relatively thorough assessment of monoamine-related neurochemical levels across the brain in response to voluntary binge-patterned ethanol drinking, but also adds to a growing body of research questioning the utility of moderate physical activity as an intervention to curb alcohol abuse.

SUBMITTER: Buhr TJ

PROVIDER: S-EPMC7947191 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveExcessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence ad libitum alcohol intake may be incomplete. Two large studies recently linked variants in the KLB locus with levels of alcohol intake in humans. KLB encodes ?-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain.MethodsWe recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma. In addition, we measured circulating FGF21 (1-181) levels, liver stiffness, triglyceride, and other metabolic parameters in three healthy Danish men before and after consuming an average of 22.6 beers/person/day (4.4 g/kg/day of ethanol) for three days during Oktoberfest 2017 in Munich, Germany. We further correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on ad libitum alcohol intake in mice.ResultsWe show that alcohol ingestion (25.3 g or ?2.5 standard drinks) acutely increases plasma levels of FGF21 (1-181) 3.4-fold in fasting humans. We also find that binge drinking for three days at Oktoberfest is associated with a 2.1-fold increase in baseline FGF21 (1-181) levels, in contrast to minor deteriorations in metabolic and hepatic biomarkers. However, basal FGF21 (1-181) levels were not correlated with differences in alcohol-related behaviors, emotional responses, or problems in our non-alcoholic subjects. Finally, we show that once-daily injection of recombinant human FGF21 reduces ad libitum alcohol intake by 21% in mice.ConclusionsFGF21 (1-181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol intake in mice. These observations are consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans.

Project description:Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.To prospectively assess the relationship of acute alcohol responses to future binge drinking.Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.Participants recruited from the community.High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence.Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems.clinicaltrials.gov Identifier: NCT00961792.

Dataset Information

The Influence of Moderate Physical Activity on Brain Monoaminergic Responses to Binge-Patterned Alcohol Ingestion in Female Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets