Molecular mechanisms of nicotine dependence

Marcelo O. Ortells, Hugo R. Arias

Research output: Contribution to journalArticle

Abstract

Nicotine is the main psychoactive substance present in tobacco, targeting neuronal nicotinic acetylcholine receptors (AChRs). The main effects of nicotine associated with smoking are AChR activation, desensitization, and upregulation, with the subsequent modulation of the mesocorticolimbic dopaminergic system. However, there is a lack of a comprehensive explanation of their roles that effectively makes clear how nicotine dependence might be established on those grounds. Receptor upregulation is an unusual effect for a drug of abuse, because theoretically this implies less need for drug consumption. Receptor upregulation and receptor desensitization are commonly viewed as opposite, homeostatic mechanisms. We here review the available information on smoking addiction, and drugs employed as aids in smoking cessation, especially under a recently presented model of nicotine dependence. In this model both receptor upregulation and receptor desensitization are responsible for establishing a biochemical mechanism of nicotine dependence, which have an important role in starting and maintaining tobacco addiction. Basically, a conclusion of this model is that those drugs used for smoking cessation should inhibit preferentially α4β2-containing AChRs and to have a low or null ability to upregulate AChRs, as this characteristic allows the smoker to achieve downregulation without abstinence symptoms.

Original languageEnglish
Pages (from-to)75-89
Number of pages15
JournalJournal of Pediatric Biochemistry
Volume1
Issue number2
DOIs
StatePublished - 1 Jan 2010
Externally publishedYes

Keywords

  • AChR desensitization
  • AChR upregulation
  • neurotransmitter release
  • nicotine addiction
  • Nicotinic receptors

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