Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.
The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.
D000311:Adrenal Glands / Q000187:drug effects; D000315:Adrenalectomy; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D002245:Carbon Dioxide; D000431:Ethanol; D011433:Propranolol; D010100:Oxygen; D009638:Norepinephrine