Binding and functional activity of nicotinic cholinergic receptors in selected rat brain regions are increased following long-term but not short-term nicotine treatment

J Neurochem. 2004 Jul;90(1):40-9. doi: 10.1111/j.1471-4159.2004.02482.x.


Chronic nicotine exposure up-regulates neuronal nicotinic receptors, but the functional consequences for these receptors is less well understood. Following 2 weeks of nicotine or saline treatment by osmotic minipump, the functional activity of nicotinic receptors was measured by concentration-response curves for epibatidine-stimulated (86)Rb efflux. Nicotine-treated animals had a significantly higher maximal efflux in cerebral cortex and superior colliculus, but not in thalamus or interpeduncular nucleus plus medial habenula. This increase was confirmed in a separate experiment with stimulation by single concentrations of epibatidine (cortex, superior colliculus) or nicotine (cortex only). Chronic nicotine did not alter (86)Rb efflux stimulated by cytisine, an alpha3beta4-selective agonist, or by potassium chloride, in any region. Short-term (16 h) nicotine exposure caused no changes in either (86)Rb efflux or receptor binding measured with [(3)H]epibatidine. Binding was significantly increased after 2 weeks nicotine exposure in cortex, superior colliculus and thalamus, but not in interpeduncular nucleus plus medial habenula. The increases in epibatidine-stimulated (86)Rb efflux in the four regions tested was linearly correlated with the increases in [(3)H]epibatidine binding in these regions (R(2) = 0.91), suggesting that rat brain receptors up-regulated by chronic nicotine are active. These results have important consequences for understanding nicotinic receptor neurobiology in smokers and users of nicotine replacement therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography / methods
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cotinine / blood
  • Dose-Response Relationship, Drug
  • Infusion Pumps, Implantable
  • Ligands
  • Male
  • Nicotine / blood
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology
  • Protein Binding / drug effects
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Rubidium Radioisotopes / metabolism
  • Rubidium Radioisotopes / pharmacokinetics
  • Time Factors
  • Up-Regulation / drug effects


  • Bridged Bicyclo Compounds, Heterocyclic
  • Ligands
  • Nicotinic Agonists
  • Pyridines
  • Receptors, Nicotinic
  • Rubidium Radioisotopes
  • Nicotine
  • Cotinine
  • epibatidine