The role of norharman in alcohol dependence and smoking: The potential inhibitory role of norharman on the urge for alcohol and nicotine use

Durk Fekkes*, Renske Spijkermans, Inge Bongers, Regina van den Eijnden

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The aim of this study was to investigate the role of the endogenous substance norharman in processes of alcohol and nicotine or tobacco dependence in both humans and animals. For this purpose heavy smokers and excessive alcohol drinkers were recruited, and rats were made dependent on alcohol and nicotine. Plasma concentrations of norharman were measured in drug-naïve, drug-free and drug-taking situations. In addition, craving and nicotine dependence were measured in the group of heavy smokers, while in the animal studies the effect of exogenously administered norharman on the behavioural signs of alcohol and nicotine withdrawal were determined. Humans who abstained from smoking and drinking for a period of 12 h showed normal plasma levels of norharman. Resumption of smoking, but not drinking, generated elevated plasma levels of norharman, especially after smoking self-made non-filter cigarettes. Although craving after a period of abstinence was stronger in smokers with high tobacco dependence compared to those with low dependence, the plasma levels of norharman were only negatively related to craving among low nicotine-dependent smokers. From the animal experiments it was concluded that nicotine intake had no effect on plasma levels of norharman. On the other hand, withdrawal symptoms elicited in nicotine-dependent rats could be attenuated by exogenous administration of norharman. Rats made alcohol-dependent by forced intake of an ethanol-containing diet showed higher norharman levels in plasma and brain compared to alcohol-naïve rats. This increase is caused by a lower clearance of norharman by the liver of alcohol-fed rats. After stopping alcohol intake, behavioural signs of alcohol withdrawal occurred which were inhibited by pretreatment with norharman. The results indicate that norharman is involved in processes of alcohol and tobacco dependence and that this substance may be a candidate adjuvant in alleviating abstinence symptoms.

Original languageEnglish
Pages (from-to)106-118
Number of pages13
JournalJournal of Substance Use
Volume10
Issue number2-3
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant from the Netherlands Organization for Scientific Research (NWO) and the Health Research and Development Council (ZON). The authors thank Dr Susanne Cappendijk (Laboratory of Psychiatry, Erasmus Medical Centre (EMC), Rotterdam and Department of Psychology, Florida State University, Tallahassee, FL, USA) for her valuable advices concerning the animal experiments and Dr G.J.J.M. Borsboom (Department of Public Health, EMC, Rotterdam) for his advices and assistance with the statistical analyses. The authors also thank Prof. Dr H.F.L. Garretsen, Prof. Dr L. Pepplinkhuizen and Dr Dike van de Mheen for their advice during several phases of this research project. The authors appreciate Mrs Astrid van Dalen (Laboratory of Psychiatry, EMC), Mr Bert Bernard and Mr Arthur van Gameren (Department of Nuclear Medicine, EMC) for skilful assistance during the behavioural tests, and Mrs Marieke Mulder, Mrs Elly Taal and Mrs Ans Voskuilen (Laboratory of Psychiatry, EMC) for performing the biochemical determinations. Finally, the authors are grateful to all volunteers who participated in this study.

Funding

This study was supported by a grant from the Netherlands Organization for Scientific Research (NWO) and the Health Research and Development Council (ZON). The authors thank Dr Susanne Cappendijk (Laboratory of Psychiatry, Erasmus Medical Centre (EMC), Rotterdam and Department of Psychology, Florida State University, Tallahassee, FL, USA) for her valuable advices concerning the animal experiments and Dr G.J.J.M. Borsboom (Department of Public Health, EMC, Rotterdam) for his advices and assistance with the statistical analyses. The authors also thank Prof. Dr H.F.L. Garretsen, Prof. Dr L. Pepplinkhuizen and Dr Dike van de Mheen for their advice during several phases of this research project. The authors appreciate Mrs Astrid van Dalen (Laboratory of Psychiatry, EMC), Mr Bert Bernard and Mr Arthur van Gameren (Department of Nuclear Medicine, EMC) for skilful assistance during the behavioural tests, and Mrs Marieke Mulder, Mrs Elly Taal and Mrs Ans Voskuilen (Laboratory of Psychiatry, EMC) for performing the biochemical determinations. Finally, the authors are grateful to all volunteers who participated in this study.

Keywords

  • Alcohol dependence
  • Nicotine dependence
  • Norharman
  • Smoking

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