Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla

Background: Ethanol modulates glutamate and gamma-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.