ETHANOL ALTERS THE CONCENTRATION OF MET-ENKEPHALIN IN BRAIN BY AFFECTING PEPTIDE-TRANSPORT SYSTEM-1 INDEPENDENT OF PREPROENKEPHALIN MESSENGER-RNA

Alcohol-related events have been proposed to be under neurochemical co ntrol, For example, the concentration of methionine enkephalin (Met-en kephalin) in brain has been inversely correlated with ethanol consumpt ion in alcohol-preferring and alcohol-nonpreferring mice, The concentr ations of Met-enkephalin are controlled in part by peptide transport s ystem-1 (PTS-1), a brain-to-blood transport system for Metenkephalin l ocated at the blood-brain barrier, We examined the relationships among concentrations of Met-enkephalin, preproenkephalin (PPE) mRNA, and PT S-1 activity in mice exposed to ethanol, PTS-1 activity decreased prog ressively 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-enke phalin tended to move in the opposite direction from PTS-1 activity, i ncreasing 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 reco very, no longer correlating with concentrations of Met-enkephalin. The se results suggest that ethanol affects concentrations of Met-enkephal in in brain through post-transcriptional mechanisms and that PTS-1 act ivity is one of those mechanisms. (C) 1997 Wiley-Liss, Inc.