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Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.

Publication ,  Journal Article
Zerrate, MC; Pletnikov, M; Connors, SL; Vargas, DL; Seidler, FJ; Zimmerman, AW; Slotkin, TA; Pardo, CA
Published in: J Pharmacol Exp Ther
July 2007

Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.

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Published In

J Pharmacol Exp Ther

DOI

ISSN

0022-3565

Publication Date

July 2007

Volume

322

Issue

1

Start / End Page

16 / 22

Location

United States

Related Subject Headings

  • Terbutaline
  • Reflex, Startle
  • Receptors, Adrenergic, beta-2
  • Rats, Sprague-Dawley
  • Rats
  • Pharmacology & Pharmacy
  • Motor Activity
  • Microglia
  • Male
  • Female
 

Citation

APA
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MLA
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Zerrate, M. C., Pletnikov, M., Connors, S. L., Vargas, D. L., Seidler, F. J., Zimmerman, A. W., … Pardo, C. A. (2007). Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. J Pharmacol Exp Ther, 322(1), 16–22. https://doi.org/10.1124/jpet.107.121483
Zerrate, M. C., M. Pletnikov, S. L. Connors, D. L. Vargas, F. J. Seidler, A. W. Zimmerman, T. A. Slotkin, and C. A. Pardo. “Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.J Pharmacol Exp Ther 322, no. 1 (July 2007): 16–22. https://doi.org/10.1124/jpet.107.121483.
Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, et al. Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. J Pharmacol Exp Ther. 2007 Jul;322(1):16–22.
Zerrate, M. C., et al. “Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.J Pharmacol Exp Ther, vol. 322, no. 1, July 2007, pp. 16–22. Pubmed, doi:10.1124/jpet.107.121483.
Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, Slotkin TA, Pardo CA. Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. J Pharmacol Exp Ther. 2007 Jul;322(1):16–22.

Published In

J Pharmacol Exp Ther

DOI

ISSN

0022-3565

Publication Date

July 2007

Volume

322

Issue

1

Start / End Page

16 / 22

Location

United States

Related Subject Headings

  • Terbutaline
  • Reflex, Startle
  • Receptors, Adrenergic, beta-2
  • Rats, Sprague-Dawley
  • Rats
  • Pharmacology & Pharmacy
  • Motor Activity
  • Microglia
  • Male
  • Female