We examined the effects of ethanol ingestion to rats on levels of the β-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.

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doi.org/10.1016/j.euroneuro.2003.10.007, hdl.handle.net/1765/31811
European Neuropsychopharmacology
Erasmus MC: University Medical Center Rotterdam

Fekkes, D., Bernard, B., & Cappendijk, S. (2004). Norharman and alcohol-dependency in male Wistar rats. European Neuropsychopharmacology, 14(5), 361–366. doi:10.1016/j.euroneuro.2003.10.007