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Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats.

Publication ,  Journal Article
Slotkin, TA; Seidler, FJ
Published in: Brain Res Bull
July 12, 2007

Developmental exposure to unrelated neurotoxicants can nevertheless converge on common final targets so as to exacerbate damage or functional deficits. We examined the effects of developmental exposure to terbutaline, a beta2-adrenergic receptor agonist used to arrest preterm labor, and chlorpyrifos, a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and chlorpyrifos (5 mg/kg) on PN11-14, with assessments conducted in juvenile and adolescent stages (PN21, PN30 and PN45), comparing each agent alone as well as sequential administration of both. By itself, terbutaline produced persistent 5HT presynaptic hyperactivity as evidenced by increased 5HT turnover in brain regions containing 5HT terminal zones; this effect was similar to that seen in earlier studies with chlorpyrifos administration during the same early postnatal period. Later administration of chlorpyrifos (PN11-14) produced a transient increase in 5HT turnover during the juvenile stage, and the sequential exposure paradigm, terbutaline followed by chlorpyrifos, showed a corresponding increase in effect over either agent alone. In combination with our earlier work on 5HT receptors, these results indicate that terbutaline is a developmental neurotoxicant that targets the 5HT system, findings that lend a mechanistic underpinning to clinical indications of elevated childhood psychiatric disorders in the offspring of women treated with beta-agonist tocolytics. Equally importantly, the interaction between terbutaline and chlorpyrifos suggests that tocolytic therapy may alter the subsequent susceptibility to common environmental toxicants.

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Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

July 12, 2007

Volume

73

Issue

4-6

Start / End Page

301 / 309

Location

United States

Related Subject Headings

  • Tocolytic Agents
  • Terbutaline
  • Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Presynaptic Terminals
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurology & Neurosurgery
 

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Slotkin, T. A., & Seidler, F. J. (2007). Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats. Brain Res Bull, 73(4–6), 301–309. https://doi.org/10.1016/j.brainresbull.2007.04.004
Slotkin, Theodore A., and Frederic J. Seidler. “Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats.Brain Res Bull 73, no. 4–6 (July 12, 2007): 301–9. https://doi.org/10.1016/j.brainresbull.2007.04.004.
Slotkin, Theodore A., and Frederic J. Seidler. “Developmental exposure to terbutaline and chlorpyrifos, separately or sequentially, elicits presynaptic serotonergic hyperactivity in juvenile and adolescent rats.Brain Res Bull, vol. 73, no. 4–6, July 2007, pp. 301–09. Pubmed, doi:10.1016/j.brainresbull.2007.04.004.
Journal cover image

Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

July 12, 2007

Volume

73

Issue

4-6

Start / End Page

301 / 309

Location

United States

Related Subject Headings

  • Tocolytic Agents
  • Terbutaline
  • Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Presynaptic Terminals
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurology & Neurosurgery