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Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems.

Publication ,  Journal Article
Slotkin, TA; Kreider, ML; Tate, CA; Seidler, FJ
Published in: Neuropsychopharmacology
May 2006

Glucocorticoid administration to preterm infants is associated with neurodevelopmental disorders. We treated developing rats with dexamethasone (Dex) at 0.05, 0.2, or 0.8 mg/kg, doses below or spanning the range in clinical use, testing the effects of administration during three different stages: gestational days 17-19, postnatal days 1-3 or postnatal days 7-9. In adulthood, we assessed the impact on synaptic biomarkers for serotonin (5-hydroxytryptamine (5HT)) systems. Across all three regimens, Dex administration evoked upregulation of cerebrocortical 5HT1A and 5HT2 receptors and the presynaptic 5HT transporter, greatest for 5HT1A receptors. The effects were fully evident even at the lowest dose. In contrast, 5HT levels in the cerebral cortex and hippocampus showed disparate patterns of temporal sensitivity, with no change after gestational treatment, an increase with the early postnatal regimen, and a decrease with the later postnatal exposure. None of the changes in 5HT concentrations were offset by adaptive changes in the fractional 5HT turnover rate. Furthermore, the critical period of sensitivity seen for 5HT levels differed from that of dopamine even within the same brain region. These findings suggest that developmental exposure to Dex during the critical neurodevelopmental period corresponding to its use in preterm infants, elicits selective changes in 5HT and dopaminergic synaptic function over and above its effects on general aspects of neural cell development, below the threshold for somatic growth impairment, and even at doses below those used clinically. Accordingly, adverse neurobehavioral consequences may be inescapable in glucocorticoid therapy of preterm infants.

Duke Scholars

Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

May 2006

Volume

31

Issue

5

Start / End Page

904 / 911

Location

England

Related Subject Headings

  • Up-Regulation
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurons
 

Citation

APA
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Slotkin, T. A., Kreider, M. L., Tate, C. A., & Seidler, F. J. (2006). Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology, 31(5), 904–911. https://doi.org/10.1038/sj.npp.1300892
Slotkin, Theodore A., Marisa L. Kreider, Charlotte A. Tate, and Frederic J. Seidler. “Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems.Neuropsychopharmacology 31, no. 5 (May 2006): 904–11. https://doi.org/10.1038/sj.npp.1300892.
Slotkin TA, Kreider ML, Tate CA, Seidler FJ. Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology. 2006 May;31(5):904–11.
Slotkin, Theodore A., et al. “Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems.Neuropsychopharmacology, vol. 31, no. 5, May 2006, pp. 904–11. Pubmed, doi:10.1038/sj.npp.1300892.
Slotkin TA, Kreider ML, Tate CA, Seidler FJ. Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology. 2006 May;31(5):904–911.
Journal cover image

Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

May 2006

Volume

31

Issue

5

Start / End Page

904 / 911

Location

England

Related Subject Headings

  • Up-Regulation
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurons