title: In vivo evidence for alcohol-induced neurochemical changes in rat brain without protracted withdrawal, pronounced thiamine deficiency, or severe liver damage.
abstract: Magnetic resonance spectroscopy (MRS) studies in human alcoholics report decreases in N-acetylaspartate (NAA) and choline-containing (Cho) compounds. Whether alterations in brain metabolite levels are attributable to alcohol per se or to physiological effects of protracted withdrawal or impaired nutritional or liver status remains unclear. Longitudinal effects of alcohol on brain metabolites measured in basal ganglia with single-voxel MRS were investigated in sibling pairs of wild-type Wistar rats, with one rat per pair exposed to escalating doses of vaporized alcohol, the other to vapor chamber air. MRS was conducted before alcohol exposure and twice during exposure. After 16 weeks of alcohol exposure, rats achieved average blood alcohol levels (BALs) of approximately 293 mg per 100 ml and had higher Cho and a trend for higher glutamine+glutamate (Glx) than controls. After 24 weeks of alcohol exposure, BALs rose to approximately 445 mg per 100 ml, and alcohol-exposed rats had higher Cho, Glx, and glutamate than controls. Thiamine and thiamine monophosphate levels were significantly lower in the alcohol than the control group but did not reach levels low enough to be considered clinically relevant. Histologically, livers of alcohol-exposed rats exhibited greater steatosis and lower glycogenosis than controls, but were not cirrhotic. This study demonstrates a specific pattern of neurobiochemical changes suggesting excessive membrane turnover or inflammation, indicated by high Cho, and alterations to glutamate homeostasis in the rat brain in response to extended vaporized alcohol exposure. Thus, we provide novel in vivo evidence for alcohol exposure as causing changes in brain chemistry in the absence of protracted withdrawal, pronounced thiamine deficiency, or severe liver damage.
authors.affiliation: Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5723, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Zahr
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Shara
authors.initials: S
authors.lastname: Vinco
authors.forename: Juan
authors.initials: J
authors.lastname: Orduna
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005234:Fatty Liver / Q000139:chemically induced; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006008:Glycogen Storage Disease / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013831:Thiamine / Q000097:blood; D013832:Thiamine Deficiency; D013833:Thiamine Monophosphate / Q000097:blood
chemical_list: D005973:Glutamine; D000431:Ethanol; D018698:Glutamic Acid; D013833:Thiamine Monophosphate; D002794:Choline; D013831:Thiamine