Repeated-Binge Ethanol Intoxication Leads to Lower Choline-Containing Compound Signals in Adult Rats: An In Vivo Marker of Ethanol-Induced Neurochemical Abnormalities

Abstract

Ethanol is the most commonly abused intoxicating substance among young and middle-aged adults, and ranks highly as a cause of disability and mortality. A pattern of heavy consumption, called binge drinking, leads to various psychiatric disorders. However, to the best of our knowledge, assessments of the influence of short-term binge ethanol (SBE) intoxication on cerebral metabolite changes in human and rat models are scarce. We used in vivo 1H magnetic resonance spectroscopy (1H-MRS) to quantitatively assess neurochemical responses in hippocampus in a rat model of SBE intoxication. Seven SBE-exposed rats received an initial dose of 5.0-g/kg ethanol (30 %-w/v solution) through gavage and additional doses of 2.0-g/kg ethanol (25 %-w/v solution), every 8 hour for 4 days. Six rats in sham control group (CNTL) received an equivalent volume of distilled water at comparable times. Sixty minutes after last gavage session, in vivo 1H-MRS scans were obtained from all rats using a 4.7 Tesla animal scanner. For neurochemical analysis, a single voxel was positioned in the hippocampal region and spectra were fitted for the quantification of 17 cerebral neurochemical signals. In hippocampus, the concentration of total choline-containing compound signals (tCho: [glycerophosphocholine] + [phosphocholine]) was significantly lower in SBE-exposed rats than in CNTL rats. Moreover, gamma-aminobutyric acid (GABA)/total creatine (tCr: creatine + phosphocreatine), tCho/tCr, and tCho/total N-acetyl-aspartate (tNAA: N-acetyl-aspartate + N-acetyl-aspartyl-glutamate) ratios were significantly lower in SBE-exposed rats than CNTL rats. We determined that tCho, GABA, and tNAA signals were highly sensitive to short-term binge ethanol intoxication, which provides insights into neurochemical alterations associated with ethanol abuse.