Intravenous ethanol infusion decreases human cortical γ-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla

Abstract

Background: Ethanol modulates glutamate and γ-aminobutyric (GABA) function. However, little is known about the acute pharmacologic effects of ethanol on levels of GABA, glutamate, and other metabolites measurable in the human cortex in vivo with proton magnetic resonance spectroscopy ((1)H-MRS).

Methods: Eleven healthy social drinkers received two intravenous ethanol infusions that raised breath alcohol levels to a clamped plateau of 60 mg/dL over 60-70 min. The first infusion established tolerability of the procedure, and the second procedure, conducted 15 ± 12 days later, was performed during (1)H-MRS of occipital GABA, glutamate, and other metabolites.

Results: The time course of brain ethanol approximated that of breath ethanol, but venous ethanol lagged by approximately 7 min. The GABA fell 13 ± 8% after 5 min of the ethanol infusion and remained reduced (p = .003) throughout the measurement. The combination of N-acetylaspartate and N-acetylaspartyl glutamate (summed as NAA) fell steadily during the infusion by 8 ± 3% (p = .0036).

Conclusions: Ethanol reduced cortical GABA and NAA levels in humans. Reductions in GABA levels are consistent with facilitation of GABA(A) receptor function by ethanol. The gradual decline in NAA levels suggests inhibition of neural or metabolic activity in the brain.

Conflict of interest statement

All other authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Breath alcohol concentrations (BAC; diamonds) from subjects during continuous infusions of ethanol 6% (v/v) compared to the desired profile (solid line). Breath samples were obtained every minute until the plateau was reached and then every 1–2 minutes thereafter for the duration of the experiment.

Figure 2

Spectra obtained before (A) and during (B) IV administration of ethanol show resonances that include GABA and ethanol. In each set, the upper spectrum represents the subspectrum obtained without the J-editing pulse applied, and the lower spectrum shows the difference spectrum where ethanol and GABA are clearly visible. Figures C and D show the time courses of GABA and NAA over the course of the ethanol infusion. (****p

Figure 3

Time courses of brain metabolites before (t=0) and during the ethanol clamp. (****p

Figure 4

Average time courses of ethanol observed in the brain, breath, and blood during the IV alcohol infusions.

Figure 5

(A) Number of drinks perceived by the subjects over time during the infusion. (B) Relationship between the perceived number of drinks at 10 minutes and the level of glutamate at 15 minutes, which is actually the glutamate signal averaged from 10 to 20 minutes (R2=0.74; p=0.0014).