Nicotine self-administration impairs hippocampal plasticity

J Neurosci. 2002 May 1;22(9):3656-62. doi: 10.1523/JNEUROSCI.22-09-03656.2002.


Nicotine, the neuroactive compound responsible for tobacco addiction, is primarily believed to have beneficial effects on the adult brain. However, in heavy smokers, abstinence from nicotine is accompanied by cognitive impairments that suggest adverse effects of nicotine on brain plasticity. For this reason, we studied changes in plasticity-related processes in the dentate gyrus (DG) of the hippocampal formation of animals trained to self-administer nicotine. The DG was chosen because it undergoes profound plastic rearrangements, many of which have been related to memory and learning performances. In this region, we examined the expression of the polysialylated (PSA) forms of neural cell adhesion molecule (NCAM), PSA-NCAM, neurogenesis, and cell death by measuring the number of pyknotic cells. It was found that nicotine self-administration profoundly decreased, in a dose-dependent manner, the expression of PSA-NCAM in the DG; a significant effect was observed at all the doses tested (0.02, 0.04, and 0.08 mg/kg per infusion). Neurogenesis was also decreased in the DG, but a significant effect was observed only for the two highest doses of nicotine. Finally, the same doses that decreased neurogenesis also increased cell death. These results raise an important additional concern for the health consequences of nicotine abuse and open new insight on the possible neural mechanisms of tobacco addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Bromodeoxyuridine
  • Cell Count
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dose-Response Relationship, Drug
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Infusions, Intravenous
  • Lateral Ventricles / cytology
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / metabolism
  • Male
  • Neural Cell Adhesion Molecule L1*
  • Neural Cell Adhesion Molecules / biosynthesis
  • Neuronal Plasticity / drug effects*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nicotine / administration & dosage*
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Sialic Acids / biosynthesis


  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • Sialic Acids
  • polysialyl neural cell adhesion molecule
  • Nicotine
  • Bromodeoxyuridine