Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study

Abstract

Background: Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals.

Methods: Twenty-four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm3 ), voxel-level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7).

Results: Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p < 0.001).

Conclusions: Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.

Keywords: Acetate; Alcohol; Cerebral Blood Flow; Thalamus.

Conflict of interest statement

Conflict of Interest

Dr. Tabakoff is founder and CEO of Lohocla Research Corporation and Dr. Hoffman is an employee of Lohocla Research Corporation (U44AA024905, UG3DA047680). The reported work is independent of, and in no conflict with work performed for Lohocla. All other authors report no conflict of interest.

© 2019 by the Research Society on Alcoholism.

Figures

Figure 1.

Study timeline. BD=blood draw, BrAC=Breath alcohol concentration measured with breathalyzer, SHAS7=Subjective High Assessment Scale 7.

Figure 2.

Compared to placebo, alcohol and acetate were associated with a significant increase in acetate levels. Values are mean, error bars are standard deviation

Figure 3.

Statistical parametric maps of the paired t-tests overlaid on a standard template. Upper two rows: compared to placebo, acetate was associated with increased CBF in medial thalamus and left parietal cortex. Lower two rows: compared to placebo, alcohol was associated with increased CBF in medial thalamus, right orbitofrontal cortex, medial prefrontal cortex, cingulate cortex, and hippocampus; Images are in neurological convention. Color bar=t-value. Maps were thresholded at p

Figure 4.

Plots showing bilateral thalamic CBF after placebo and after drug (acetate or alcohol). Each line represents a participant.

Figure 5.

Subjective high assessment score-7 (SHAS-7) was associated with an increase after alcohol, but not after acetate. Values are mean. Error bars are standard deviation.