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Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations.

Publication ,  Journal Article
Abreu-Villaça, Y; Seidler, FJ; Tate, CA; Slotkin, TA
Published in: Brain Res
July 25, 2003

In the fetus, nicotine is a neuroteratogen that elicits cell damage and loss and subsequent abnormalities of synaptic function. We explored whether these effects extend into adolescence, the period when most people begin smoking. Beginning on postnatal day 30, rats were given a 1 week regimen of nicotine infusions or twice-daily injections, at doses (0.6, 2 and 6 mg/kg/day) set to achieve plasma levels found in occasional to regular smokers. We assessed indices of cell packing density and cell number (DNA concentration and content), cell size (total protein/DNA ratio) and neuritic projections (membrane/total protein) in the midbrain, hippocampus and cerebral cortex, three regions known to be vulnerable to developmental effects of nicotine. With either route of administration, nicotine evoked shortfalls in DNA concentration and content, compensatory elevations of total protein/DNA, and reductions in the membrane/total protein ratio. Nearly all of the effects were apparent even at the lowest dose of nicotine and remained fully evident 1 month posttreatment. Although both males and females showed significant alterations, in general the effects were larger in females. Our results indicate that in adolescence, even a brief period of continuous or intermittent nicotine exposure, elicits lasting alterations in biomarkers associated with cellular and neuritic damage. As the effects are detected at exposures that produce plasma concentrations one-tenth of those in regular smokers, the exquisite sensitivity of the adolescent brain to nicotine neurotoxicity may contribute to lasting neurobehavioral damage even in occasional smokers.

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Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

July 25, 2003

Volume

979

Issue

1-2

Start / End Page

114 / 128

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Sex Characteristics
  • Rats, Sprague-Dawley
  • Rats
  • Nicotine
  • Neurotoxins
  • Neurology & Neurosurgery
  • Neurofilament Proteins
  • Neurites
  • Male
 

Citation

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Abreu-Villaça, Y., Seidler, F. J., Tate, C. A., & Slotkin, T. A. (2003). Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations. Brain Res, 979(1–2), 114–128. https://doi.org/10.1016/s0006-8993(03)02885-3
Abreu-Villaça, Yael, Frederic J. Seidler, Charlotte A. Tate, and Theodore A. Slotkin. “Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations.Brain Res 979, no. 1–2 (July 25, 2003): 114–28. https://doi.org/10.1016/s0006-8993(03)02885-3.
Abreu-Villaça, Yael, et al. “Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations.Brain Res, vol. 979, no. 1–2, July 2003, pp. 114–28. Pubmed, doi:10.1016/s0006-8993(03)02885-3.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

July 25, 2003

Volume

979

Issue

1-2

Start / End Page

114 / 128

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Sex Characteristics
  • Rats, Sprague-Dawley
  • Rats
  • Nicotine
  • Neurotoxins
  • Neurology & Neurosurgery
  • Neurofilament Proteins
  • Neurites
  • Male