An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions.

Published

Journal Article

Nearly all smokers begin tobacco use in adolescence, and approximately 25% of US teenagers are daily smokers. Prenatal nicotine exposure is known to produce brain damage, to alter synaptic function and to cause behavioral anomalies, but little or no work has been done to determine if the adolescent brain is also vulnerable. We examined the effect of adolescent nicotine exposure on indices of cell damage in male and female rats with an infusion paradigm designed to match the plasma levels found in human smokers or in users of the transdermal nicotine patch. Measurements were made of DNA and protein as well as expression of mRNAs encoding genes involved in differentiation and apoptosis (p53, c-fos) in cerebral cortex, midbrain and hippocampus. Following nicotine treatment from postnatal days 30-47.5, changes in macromolecular constituents indicative of cell loss (reduced DNA) and altered cell size (protein/DNA ratio) were seen across all three brain regions. In addition, expression of p53 showed region- and gender-selective alterations consistent with cell damage; c-fos, which is constitutively overexpressed after gestational nicotine exposure, was unaffected with the adolescent treatment paradigm. Although these measures indicate that the fetal brain is more vulnerable to nicotine than is the adolescent brain, the critical period for nicotine-induced developmental neurotoxicity clearly extends into adolescence. Effects on gene expression and cell number, along with resultant or direct effects on synaptic function, may contribute to increased addictive properties and long-term behavioral deficits.

Full Text

Duke Authors

Cited Authors

  • Trauth, JA; Seidler, FJ; Slotkin, TA

Published Date

  • June 9, 2000

Published In

Volume / Issue

  • 867 / 1-2

Start / End Page

  • 29 - 39

PubMed ID

  • 10837795

Pubmed Central ID

  • 10837795

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/s0006-8993(00)02208-3

Language

  • eng

Conference Location

  • Netherlands