Effects of chronic ethanol on brain and serum level of methionine enkephalin

Most evidence agrees that levels of methionine enkephalin (Met-Enk) in brain are inversely correlated with ethanol drinking and withdrawal seizures. One area of discrepancy is the effect of chronic ethanol administration on the level of immunoactive Met-Enk in brain, with some authors reporting increased and others reporting decreased levels. These reports differed greatly in terms of method of ethanol administration, species used, length of time ethanol was administered, and the region of brain examined. We found that all studies could be resolved by considering only length of time ethanol was administered, with Met-Enk levels first increasing and then decreasing. We tested this finding by determining the effect of 4-56 days of ethanol delivered in liquid feed on levels of brain Met-Enk. We found that brain levels of Met-Enk peaked after 7 days of ethanol ingestion and declined to levels lower than control by 28 days. Exposure to ethanol abolished a correlation between brain and serum levels of Met-Enk which occurred in controls. HPLC showed that whereas 100% of immunoactivity eluted in the position of Met-Enk in controls, only about 50% eluted as Met-Enk in mice exposed to ethanol. These results support the hypothesis that exposure to ethanol alters brain Met-Enk in a way consistent with the reinforcement of physical dependence.