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Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Levin, ED; Seidler, FJ
Published in: Brain Res Bull
February 2015

Nicotine and chlorpyrifos are developmental neurotoxicants that target serotonin systems. We examined whether prenatal nicotine exposure alters the subsequent response to chlorpyrifos given postnatally. Pregnant rats received nicotine throughout gestation at 3mg/kg/day, a regimen designed to achieve plasma levels seen in smokers; chlorpyrifos was given to pups on postnatal days (PN) 1-4 at 1mg/kg, just above the detection threshold for brain cholinesterase inhibition. We assessed long-term effects from adolescence (PN30) through full adulthood (PN150), measuring the expression of serotonin receptors and serotonin turnover (index of presynaptic impulse activity) in cerebrocortical brain regions encompassing the projections that are known targets for nicotine and chlorpyrifos. Nicotine or chlorpyrifos individually increased the expression of serotonin receptors, with greater effects on males than on females and with distinct temporal and regional patterns indicative of adaptive synaptic changes rather than simply an extension of initial injury. This interpretation was confirmed by our finding an increase in serotonin turnover, connoting presynaptic serotonergic hyperactivity. Animals receiving the combined treatment showed a reduction in these adaptive effects on receptor binding and turnover relative to the individual agents, or even an effect in the opposite direction; further, normal sex differences in serotonin receptor concentrations were dissipated or reversed, an effect that was confirmed by behavioral evaluations in the Novel Objection Recognition Test. In addition to the known liabilities associated with maternal smoking during pregnancy, our results point to additional costs in the form of heightened vulnerability to neurotoxic chemicals encountered later in life.

Duke Scholars

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

February 2015

Volume

111

Start / End Page

84 / 96

Location

United States

Related Subject Headings

  • Sex Factors
  • Serotonin
  • Recognition, Psychology
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Nicotine
  • Neurology & Neurosurgery
 

Citation

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Slotkin, T. A., Skavicus, S., Levin, E. D., & Seidler, F. J. (2015). Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition. Brain Res Bull, 111, 84–96. https://doi.org/10.1016/j.brainresbull.2015.01.003
Slotkin, Theodore A., Samantha Skavicus, Edward D. Levin, and Frederic J. Seidler. “Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.Brain Res Bull 111 (February 2015): 84–96. https://doi.org/10.1016/j.brainresbull.2015.01.003.
Slotkin, Theodore A., et al. “Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.Brain Res Bull, vol. 111, Feb. 2015, pp. 84–96. Pubmed, doi:10.1016/j.brainresbull.2015.01.003.
Journal cover image

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

February 2015

Volume

111

Start / End Page

84 / 96

Location

United States

Related Subject Headings

  • Sex Factors
  • Serotonin
  • Recognition, Psychology
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Nicotine
  • Neurology & Neurosurgery