Norharman and alcohol-dependency in male Wistar rats

Eur Neuropsychopharmacol. 2004 Oct;14(5):361-6. doi: 10.1016/j.euroneuro.2003.10.007.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / drug therapy
  • Alcoholism / metabolism*
  • Animals
  • Behavior, Animal
  • Brain / drug effects
  • Brain / metabolism
  • Carbolines
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Half-Life
  • Harmine / analogs & derivatives*
  • Harmine / metabolism*
  • Harmine / therapeutic use
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / metabolism*

Substances

  • Carbolines
  • Central Nervous System Depressants
  • Ethanol
  • Harmine
  • norharman