Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide transport system-1 independent of preproenkephalin mRNA

Abstract

Alcohol-related events have been proposed to be under neurochemical control. For example, the concentration of methionine enkephalin (Met-enkephalin) in brain has been inversely correlated with ethanol consumption in alcohol-preferring and alcohol-nonpreferring mice. The concentrations of Met-enkephalin are controlled in part by peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin located at the blood-brain barrier. We examined the relationships among concentrations of Met-enkephalin, preproenkephalin (PPE) mRNA, and PTS-1 activity in mice exposed to ethanol. PTS-1 activity decreased progressively during the process of addiction and then partially recovered within hours after withdrawal of ethanol. Serotonin lost its ability to modulate PTS-1 activity in exposed mice, indicating that regulation of PTS-1 activity was affected by ethanol. Concentrations of Met-enkephalin tended to move in the opposite direction from PTS-1 activity, increasing significantly with addiction. In naive mice, PPE mRNA levels correlated with the concentrations of Met-enkephalin. However, levels of PPE mRNA remained unchanged during addiction, withdrawal, and recovery, no longer correlating with concentrations of Met-enkephalin. These results suggest that ethanol affects concentrations of Met-enkephalin in brain through post-transcriptional mechanisms and that PTS-1 activity is one of those mechanisms.