Sensorimotor deficits and increased brain nicotinic acetylcholine receptors following exposure to chlorpyrifos and/or nicotine in rats

Mohamed B. Abou-Donia, Ali Abdel-Rahman, Larry B. Goldstein, Anjelika M. Dechkovskaia, Deepti U. Shah, Sarah L. Bullman, Wasiuddin A. Khan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Despite well-known adverse effects associated with cigarette smoking, approximately 20% of the US population continues to smoke and many more are exposed to environmental tobacco smoke. Many of the same individuals are also exposed to environmental neurotoxic chemicals such as the organophosphorus insecticide chlorpyrifos. In the present study, the effects of exposure to low doses of nicotine and chlorpyrifos alone and in combination, were studied on the central cholinergic system and sensorimotor performance in rats. Male Sprague-Dawley rats (250-300 g) were treated with nicotine (1 mg/kg s.c., in normal saline), chlorpyrifos (0.1 mg/kg dermally, in 0.1 ml 70% ethanol), or a combination of both, daily for 30 days. Control rats were treated with saline and dermally with ethanol. Sensorimotor behavior was evaluated 24 h following the last dose using a battery of tests. There was a significant deficit in incline plane performance, beam-walk score and beam-walk time following exposure to each chemical, alone or in combination. The deficit in incline plane performance was greater when the two chemicals were given in combination than with either compound alone. Biochemical analysis showed a decrease in cerebellar and an increase in midbrain acetyl-cholinesterase (ACHE) activity following combined exposure. Exposure to nicotine alone resulted in a significant increase in AChE activity in brainstem and midbrain, whereas there was no significant change after exposure to chlorpyrifos, alone. A significant increase in ligand binding to nicotinic acetylcholine receptors (nAChR) was observed in brainstem and cortex following exposure to nicotine or chlorpyrifos. This was further augmented with combined exposure, which caused a modest but significant increase in m2 muscarinic acetylcholine receptors (m2-mAChR) ligand binding in the cortex. These data suggest that exposure to either nicotine or chlorpyrifos or a combination of the two may impair neurobehavioral performance and affect the central nervous system cholinergic pathways.

Original languageEnglish
Pages (from-to)452-458
Number of pages7
JournalArchives of Toxicology
Issue number8
StatePublished - Aug 1 2003

Bibliographical note

Funding Information:
Acknowledgements This study was supported in part by an US Environmental Protection Agency (EPA) grant R829399-01-0. The views, opinion and/or findings contained in this report are those of the authors and should not be construed as an official US EPA policy or decision unless so designated by other documents.


  • Acetylcholinesterase
  • Central nervous system
  • Chlorpyrifos
  • Combined exposure
  • Muscarinic acetylcholine receptor
  • Neurotoxicity
  • Nicotine
  • Nicotinic acetylcholine receptor
  • Organophosphorus Insecticides
  • Sensorimotor
  • Smoking

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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