MODULATION BY ALCOHOL AND METHADONE OF 2-DEOXYGLUCOSE-STIMULATED PANCREATIC-SECRETION IN THE RAT

Alcohol intake is a major problem in drug addicts, and it is not clear whether the Effects of alcohol and opiates are additive or potentiati ng. Vagally stimulated pancreatic secretion in rats is potently inhibi ted by opiates acting centrally at mu-receptors. In the present experi ments, we determined the effects of methadone on 2-deoxyglucose (2DG)- stimulated pancreatic secretion in rats treated with acute (1.9 g/kg-3 h, intravenously) or chronic (1 or 3 month drinking) ethanol. In both acute and 1 month chronic alcoholic rats, methadone administered at i ts 50% inhibitory dose (ID50) reduced by about 50% 2DG-stimulated panc reatic secretion of sodium, bicarbonate and protein, and ethanol had o nly faint, nonsignificant inhibitory effects. In 3 month chronic alcoh olic rats, similar results were obtained, but methadone inhibited 2DG- stimulated pancreatic secretion by 60 to 90% in these older mts. No si gnificant interaction was found in any condition between ethanol and m ethadone, suggesting that they had only additive, but not potentiating effects in this model.