The permissive role of glucocorticoids in the development of ethanol dependence and tolerance.
In mice chronically treated with ethanol (in a liquid diet containing 6% ethanol ad libitum for 2 weeks), brain tryptophan hydroxylase (TPH) activity was increased (by 30-45% in whole brain), while brain tyrosine hydroxylase activity remained unchanged. Such chronic ethanol treatment also induced susceptibility to audiogenic seizures during withdrawal (60% incidence). When ethanol treatment was given to adrenalectomized (Adx) mice, the increase of brain TPH activity and the development of withdrawal audiogenic seizures were both prevented. In Adx mice receiving daily injections of corticosterone (0.5 mg/mouse), the ethanol-induced increase of brain TPH activity and the occurrence of withdrawal audiogenic seizures were both restored. Similarly, the ethanol-induced increase of liver alcohol dehydrogenase activity (by 60%) was prevented in Adx mice and restored by corticosterone replacement. It was noted that in all three cases replacement with such large doses of the corticoid did not enhance the ethanol effects, but merely restored the effects to the levels observed in intact mice. Apparently, glucocorticoids are required in a permissive role in order for the ethanol effects to occur.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000315:Adrenalectomy; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000437:Alcoholism / Q000201:enzymology / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D003345:Corticosterone / Q000502:physiology; D004361:Drug Tolerance; D004569:Electroencephalography; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012110:Reserpine / Q000494:pharmacology; D012640:Seizures / Q000201:enzymology; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000503:physiopathology; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005938:Glucocorticoids; D000431:Ethanol; D012110:Reserpine; D006916:5-Hydroxytryptophan; D000429:Alcohol Oxidoreductases; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D003345:Corticosterone; D006854:Hydrocortisone