Ethanol treatment alters β-endorphin metabolism by purified synaptosomal plasma membranes

Ethanol administration has been shown to affect β-endorphin (β-E) levels in most brain areas. Chronic ethanol treatment has also lead to changes in the levels of Met- and Leu-enkephalin which may be due to the recent finding that enkephalinase A activity is significantly altered. To determine if proteolytic enzymes responsible for β-E metabolism at the pSPM are also altered, we studied the effect of chronic ethanol (7% v/v; 8 days) administration on in vitro central β-E metabolism in male C57/BL mice. Purified SPM was time-course incubated with β-E (20 μM) for 30-120 min and subjected to HPLC analyses for determination of β-endorphin and related fragments. Chronic ethanol significantly reduced the half-life for β-E at the pSPM (T _{1 2}=50/min) versus controls (T _{1 2}=100.4 min). Chronic ethanol also caused significant accumulation of the behaviorally active α- and γ-type endorphins formed at the pSPM. These results suggest that chronic ethanol treatment leads to an increase in the activity of peptidases responsible for β-E metabolism at pSPM leading to an increased formation of both α- and γ-type endorphins which may affect alcohol related behaviors.