Norharman and alcohol-dependency in male Wistar rats.
We examined the effects of ethanol ingestion to rats on levels of the beta-carboline norharman in plasma, brain and liver at the end of ethanol ingestion and 10 h after withdrawal. We also investigated the effect of exogenously administered norharman on the behavioural signs of alcohol withdrawal. Ethanol was given by a liquid diet for 21 days. Norharman plasma levels in alcohol fed rats were significantly elevated compared to both control rats and to rats 10 h after withdrawal. Norharman levels in brains and livers showed a similar pattern. The capacity of the livers of both alcohol-dependent and withdrawal rats to catabolise norharman was significantly reduced compared to control rats. Norharman injected intraperitoneally (6.3 mg/kg) attenuated the behavioural signs of alcohol withdrawal significantly. The mechanism behind the increased norharman levels in alcohol-dependent rats may be inhibition of the synthesis and/or activity of liver enzyme(s) responsible for the breakdown of norharman.
Fekkes
Durk
D
Department of Psychiatry, Laboratory of Psychiatry, room Ee 1438, Erasmus University Medical Centre, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. d.fekkes@erasmusmc.nl
Bernard
Bert F
BF
Cappendijk
Susanne L T
SL
D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002243:Carbolines; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006207:Half-Life; D006247:Harmine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism*
D002243:Carbolines; D002492:Central Nervous System Depressants; D000431:Ethanol; D006247:Harmine; C010262:norharman