Rapid delivery of nicotine promotes behavioral sensitization and alters its neurobiological impact

Biol Psychiatry. 2005 Feb 15;57(4):351-60. doi: 10.1016/j.biopsych.2004.11.040.


Background: Nicotine is highly addictive when it is inhaled from tobacco smoke, whereas nicotine replacement products, which usually deliver nicotine orally or transdermally, rarely lead to addiction. It has been proposed that this is due in part to differences in the rate of nicotine delivery to the brain under the two conditions. However, the mechanism by which rapid nicotine delivery facilitates the transition to addiction is not known. The ability of drugs to alter gene regulation and to produce sensitization has been implicated in addiction. We hypothesized, therefore, that varying the rate of nicotine administration may modulate its ability to elicit this form of plasticity.

Methods: Animals were treated with repeated intravenous infusions of nicotine over 5, 25, or 100 sec, and their locomotor responses were monitored over treatment days.

Results: We found that increasing the rate of intravenous nicotine infusion potentiated its ability to produce locomotor sensitization, and to induce c-fos and arc mRNA expression in mesocorticolimbic structures.

Conclusions: We suggest that rapid administration may increase vulnerability to addiction by altering the neurobiological impact of nicotine and promoting a form of neurobehavioral plasticity (i.e., sensitization) that can lead to pathological incentive motivation for drugs.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Cell Count / methods
  • Cytoskeletal Proteins
  • Drug Administration Schedule
  • Female
  • Gene Expression Regulation / drug effects*
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • In Situ Hybridization / methods
  • Infusions, Intravenous / methods
  • Motor Activity / drug effects*
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Cytoskeletal Proteins
  • Immediate-Early Proteins
  • Nerve Tissue Proteins
  • Nicotinic Agonists
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • activity regulated cytoskeletal-associated protein
  • Nicotine