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Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Card, J; Stadler, A; Levin, ED; Seidler, FJ
Published in: Toxicol Sci
September 2015

Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage.

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Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

September 2015

Volume

147

Issue

1

Start / End Page

178 / 189

Location

United States

Related Subject Headings

  • Up-Regulation
  • Toxicology
  • Synapses
  • Smoke
  • Sex Characteristics
  • Serotonin
  • Serotonergic Neurons
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
 

Citation

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Slotkin, T. A., Skavicus, S., Card, J., Stadler, A., Levin, E. D., & Seidler, F. J. (2015). Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci, 147(1), 178–189. https://doi.org/10.1093/toxsci/kfv123
Slotkin, Theodore A., Samantha Skavicus, Jennifer Card, Ashley Stadler, Edward D. Levin, and Frederic J. Seidler. “Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.Toxicol Sci 147, no. 1 (September 2015): 178–89. https://doi.org/10.1093/toxsci/kfv123.
Slotkin TA, Skavicus S, Card J, Stadler A, Levin ED, Seidler FJ. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci. 2015 Sep;147(1):178–89.
Slotkin, Theodore A., et al. “Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.Toxicol Sci, vol. 147, no. 1, Sept. 2015, pp. 178–89. Pubmed, doi:10.1093/toxsci/kfv123.
Slotkin TA, Skavicus S, Card J, Stadler A, Levin ED, Seidler FJ. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Toxicol Sci. 2015 Sep;147(1):178–189.
Journal cover image

Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

September 2015

Volume

147

Issue

1

Start / End Page

178 / 189

Location

United States

Related Subject Headings

  • Up-Regulation
  • Toxicology
  • Synapses
  • Smoke
  • Sex Characteristics
  • Serotonin
  • Serotonergic Neurons
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats