Chronic ethanol alters the receptor binding characteristics of the delta opioid receptor ligand, D-Ala2-D-Leu5 enkephalin in mouse brain.

The binding characteristics of the delta opioid receptor ligand, 3H-D-Ala2-D-Leu5 enkephalin, were markedly altered in brains obtained from mice fed an ethanol-containing diet for five days. Control mice exhibited both a high and low affinity site for 3H-D-Ala2-D-Leu5 enkephalin, whereas those consuming the ethanol diet were found to possess only one binding site. This singular site has an intermediate KD value with an increase in receptor number when compared to the high and low affinity sites observed in control mice. The in vitro addition of ethanol to a brain membrane preparation obtained from untreated mice, at a concentration equivalent to that found in the blood of the ethanol-treated mice, did not markedly affect D-Ala2-D-Leu5 enkephalin binding characteristics. No alteration in the binding characteristics of 3H-naloxone, a mu receptor ligand, was noted following five days of ethanol consumption. Mice maintained on the ethanol-containing diet were tolerant to the activity-stimulating effects of acute ethanol administration. These results suggest that mice consuming an ethanol diet in sufficient quantities to render them tolerant exhibit a specific loss of a 3H-D-Ala2-D-Leu5 enkephalin binding site, while the binding of 3H-naloxone was unchanged.