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Fetal and adolescent nicotine administration: effects on CNS serotonergic systems.

Publication ,  Journal Article
Xu, Z; Seidler, FJ; Ali, SF; Slikker, W; Slotkin, TA
Published in: Brain Res
September 28, 2001

Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the time that smoking typically commences. We administered nicotine to pregnant or adolescent rats via continuous minipump infusions, using dose rates that replicate the plasma nicotine levels found in smokers. Fetal nicotine exposure (gestational days 4-21) decreased the cerebrocortical binding of paroxetine (PXT), a marker for the serotonin (5HT) transporter, likely indicative of a decrease in nerve terminals in that region; the effect lasted into adulthood. There was a corresponding increase in PXT binding in the midbrain/brainstem, the region containing the 5HT cell bodies that project to the cerebral cortex, a pattern typical of reactive sprouting in response to nerve terminal damage. After adolescent nicotine treatment (postnatal days 30-47), PXT binding was reduced in the hippocampus and striatum instead of the cerebral cortex, again accompanied by increased binding in the midbrain and brainstem; the patterns of effects within each region were gender-selective, although both males and females displayed abnormalities. Superimposed on this overall effect, there were transient increases in PXT binding, likely due to acute stimulant effects of nicotine. We also assessed 5HT presynaptic activity (5HIAA/5HT ratio). Withdrawal from adolescent nicotine treatment led to suppression of activity in the cerebral cortex and activation in the midbrain. These results indicate that both fetal and adolescent nicotine exposure elicit apparent damage to 5HT projections with reactive increases in regions containing 5HT cell bodies. Long-term changes in 5HT innervation and/or synaptic activity may play a role in the subsequent development of depression in the offspring of women who smoke during pregnancy or in adolescent smokers.

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Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

September 28, 2001

Volume

914

Issue

1-2

Start / End Page

166 / 178

Location

Netherlands

Related Subject Headings

  • Tobacco Use Disorder
  • Synaptic Transmission
  • Sex Characteristics
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Radioligand Assay
  • Presynaptic Terminals
  • Prenatal Exposure Delayed Effects
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, Z., Seidler, F. J., Ali, S. F., Slikker, W., & Slotkin, T. A. (2001). Fetal and adolescent nicotine administration: effects on CNS serotonergic systems. Brain Res, 914(1–2), 166–178. https://doi.org/10.1016/s0006-8993(01)02797-4
Xu, Z., F. J. Seidler, S. F. Ali, W. Slikker, and T. A. Slotkin. “Fetal and adolescent nicotine administration: effects on CNS serotonergic systems.Brain Res 914, no. 1–2 (September 28, 2001): 166–78. https://doi.org/10.1016/s0006-8993(01)02797-4.
Xu Z, Seidler FJ, Ali SF, Slikker W, Slotkin TA. Fetal and adolescent nicotine administration: effects on CNS serotonergic systems. Brain Res. 2001 Sep 28;914(1–2):166–78.
Xu, Z., et al. “Fetal and adolescent nicotine administration: effects on CNS serotonergic systems.Brain Res, vol. 914, no. 1–2, Sept. 2001, pp. 166–78. Pubmed, doi:10.1016/s0006-8993(01)02797-4.
Xu Z, Seidler FJ, Ali SF, Slikker W, Slotkin TA. Fetal and adolescent nicotine administration: effects on CNS serotonergic systems. Brain Res. 2001 Sep 28;914(1–2):166–178.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

September 28, 2001

Volume

914

Issue

1-2

Start / End Page

166 / 178

Location

Netherlands

Related Subject Headings

  • Tobacco Use Disorder
  • Synaptic Transmission
  • Sex Characteristics
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Radioligand Assay
  • Presynaptic Terminals
  • Prenatal Exposure Delayed Effects