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Mode of action: disruption of brain cell replication, second messenger, and neurotransmitter systems during development leading to cognitive dysfunction--developmental neurotoxicity of nicotine.

Publication ,  Journal Article
Slikker, W; Xu, ZA; Levin, ED; Slotkin, TA
Published in: Crit Rev Toxicol
2005

Developmental exposure to nicotine in rats results in neurobehavioral effects such as reduced locomotor and cognitive function. Key events in the animal mode of action (MOA) include binding to the nicotinic cholinergic receptor during prenatal and/or early postnatal development. This leads to premature onset of cell differentiation at the expense of cell replication, which leads to brain cell death or structural alterations in regional brain areas. Other events include an initial increase followed by a decrease in adenyl cyclase activity, as well as effects on the noradrenergic, dopaminergic, and serotonergic neurotransmitter systems. Because the nicotine receptor is also present in the developing human brain and the underlying biology for DNA synthesis and cell signaling is comparable, this MOA is likely to be relevant for humans. Although the effects of nicotine exposure in developing humans is not well documented, nicotine exposure as a result of cigarette smoking during pregnancy is associated with several physiological and behavioral outcomes that are reminiscent of the effects of nicotine alone in animal models. As data become available with the advent of the use of the nicotine patch in pregnant humans, the question as to the relative importance of smoking per se versus nicotine alone may be determined.

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Published In

Crit Rev Toxicol

DOI

ISSN

1040-8444

Publication Date

2005

Volume

35

Issue

8-9

Start / End Page

703 / 711

Location

England

Related Subject Headings

  • Toxicology
  • Second Messenger Systems
  • Rats
  • Pregnancy
  • Nicotinic Agonists
  • Nicotine
  • Neurotransmitter Agents
  • Nervous System Diseases
  • Humans
  • Female
 

Citation

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Slikker, W., Xu, Z. A., Levin, E. D., & Slotkin, T. A. (2005). Mode of action: disruption of brain cell replication, second messenger, and neurotransmitter systems during development leading to cognitive dysfunction--developmental neurotoxicity of nicotine. Crit Rev Toxicol, 35(8–9), 703–711. https://doi.org/10.1080/10408440591007421
Slikker, William, Z Alex Xu, Edward D. Levin, and Theodore A. Slotkin. “Mode of action: disruption of brain cell replication, second messenger, and neurotransmitter systems during development leading to cognitive dysfunction--developmental neurotoxicity of nicotine.Crit Rev Toxicol 35, no. 8–9 (2005): 703–11. https://doi.org/10.1080/10408440591007421.
Journal cover image

Published In

Crit Rev Toxicol

DOI

ISSN

1040-8444

Publication Date

2005

Volume

35

Issue

8-9

Start / End Page

703 / 711

Location

England

Related Subject Headings

  • Toxicology
  • Second Messenger Systems
  • Rats
  • Pregnancy
  • Nicotinic Agonists
  • Nicotine
  • Neurotransmitter Agents
  • Nervous System Diseases
  • Humans
  • Female