Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study.
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.
['Tanabe|Jody|J|0000-0002-7110-8444', 'Yamamoto|Dorothy J|DJ|', 'Sutton|Brianne|B|', 'Brown|Mark S|MS|', 'Hoffman|Paula L|PL|', 'Burnham|Ellen L|EL|', 'Glueck|Deborah H|DH|', 'Tabakoff|Boris|B|0000-0001-5132-5030']
D000085:Acetates D061605:Administration, Intravenous D000284:Administration, Oral D000328:Adult D000428:Alcohol Drinking D001921:Brain D002492:Central Nervous System Depressants D002560:Cerebrovascular Circulation D000431:Ethanol D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D010865:Pilot Projects D013788:Thalamus D055815:Young Adult
Alcohol Acetate Cerebral Blood Flow Thalamus