Nicotine addiction: the possible role of functional upregulation

Trends Pharmacol Sci. 2002 Mar;23(3):130-6. doi: 10.1016/S0165-6147(00)01979-9.


Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subtypes of nAChRs, which are the most abundant subtypes in the brain, are functionally upregulated following prolonged exposure to nicotine. The possible consequences of functional upregulation for nicotine addiction are discussed. Moreover, we propose a new paradigm that describes the unusual behavior of these neuronal nAChRs and helps to explain the effects of nicotine in the CNS and the diffuse effects of ACh.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Cells, Cultured
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Nicotine / pharmacology
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism
  • Receptors, Nicotinic / physiology*
  • Smoking Cessation
  • Tobacco Use Disorder / physiopathology*
  • Up-Regulation*


  • Receptors, Nicotinic
  • Nicotine