In contrast to drugs listed above, ethanol inhibits ERK phosphorylation. Acute administration of alcohol decreases levels of p-ERK in the amygdala, dorsal striatum, cerebellum, cerebral cortex, and hippocampus.27–29 The mechanism by which ethanol reduces ERK phosphorylation is unknown. However, in rats treated chronically with ethanol, hepatic ERK phosphorylation is decreased in association with elevated levels of the lipid peroxidation product 4-hydroxynonenal, which inhibits ERK phosphorylation in vitro.30
