title: Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.
abstract: During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, nvolkow@nida.nih.gov.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Shokri Kojori
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, New York 11973-5000, and.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York 11794.
authors.forename: Helene
authors.identifier: http://orcid.org/0000-0002-2887-6667
authors.initials: H
authors.lastname: Benveniste
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D000435:Alcoholic Intoxication / Q000097:blood / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010775:Photic Stimulation; D049268:Positron-Emission Tomography; D013997:Time Factors; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D019788:Fluorodeoxyglucose F18; D000431:Ethanol; D005947:Glucose
keywords: acetate metabolism; alcoholism; glial metabolism; glycolysis; positron emission tomography