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Mimicking maternal smoking and pharmacotherapy of preterm labor: fetal nicotine exposure enhances the effect of late gestational dexamethasone treatment on noradrenergic circuits.

Publication ,  Journal Article
Slotkin, TA; Seidler, FJ
Published in: Brain Res Bull
November 25, 2011

Smoking during pregnancy increases the risk of preterm delivery, which in turn necessitates the common use of glucocorticoids to prevent respiratory distress syndrome. Accordingly, there is a substantial population exposed conjointly to fetal nicotine and glucocorticoids (typically dexamethasone). We administered nicotine to pregnant rats throughout gestation, using a regimen (3 mg/kg/day by osmotic minipump) that maintains plasma nicotine levels within the range seen in smokers; on gestational days 17, 18 and 19, we gave 0.2 mg/kg of dexamethasone. We assessed norepinephrine levels in three brain regions (frontal/parietal cortex, brainstem, cerebellum) throughout adolescence, young adulthood and later adulthood, and contrasted the persistent effects with comparable measures in peripheral tissues (heart, liver). In adolescence, males showed initial deficits in the frontal/parietal cortex with either dexamethasone alone or the combined treatment, with resolution to normal by young adulthood; the group exposed to both nicotine+dexamethasone showed subsequent elevations that emerged in full adulthood and persisted through five months of age, an effect not seen with either agent separately. In females, the combined exposure produced an initial deficit that resolved by young adulthood, without any late-emerging changes. We did not see comparable effects in the other brain regions or peripheral tissues. This indicates that nicotine exposure sensitizes the developing brain to the adverse effects of dexamethasone treatment, producing sex-selective changes in innervation and/or activity of specific noradrenergic circuits. The fact that the combined treatment produced greater effects points to potentially worsened neurobehavioral outcomes after pharmacotherapy of preterm labor in the offspring of smokers.

Duke Scholars

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

November 25, 2011

Volume

86

Issue

5-6

Start / End Page

435 / 440

Location

United States

Related Subject Headings

  • Smoking
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Obstetric Labor, Premature
  • Norepinephrine
  • Nicotinic Agonists
  • Nicotine
 

Citation

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Slotkin, T. A., & Seidler, F. J. (2011). Mimicking maternal smoking and pharmacotherapy of preterm labor: fetal nicotine exposure enhances the effect of late gestational dexamethasone treatment on noradrenergic circuits. Brain Res Bull, 86(5–6), 435–440. https://doi.org/10.1016/j.brainresbull.2011.08.009
Slotkin, Theodore A., and Frederic J. Seidler. “Mimicking maternal smoking and pharmacotherapy of preterm labor: fetal nicotine exposure enhances the effect of late gestational dexamethasone treatment on noradrenergic circuits.Brain Res Bull 86, no. 5–6 (November 25, 2011): 435–40. https://doi.org/10.1016/j.brainresbull.2011.08.009.
Slotkin, Theodore A., and Frederic J. Seidler. “Mimicking maternal smoking and pharmacotherapy of preterm labor: fetal nicotine exposure enhances the effect of late gestational dexamethasone treatment on noradrenergic circuits.Brain Res Bull, vol. 86, no. 5–6, Nov. 2011, pp. 435–40. Pubmed, doi:10.1016/j.brainresbull.2011.08.009.
Journal cover image

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

November 25, 2011

Volume

86

Issue

5-6

Start / End Page

435 / 440

Location

United States

Related Subject Headings

  • Smoking
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Obstetric Labor, Premature
  • Norepinephrine
  • Nicotinic Agonists
  • Nicotine