Co-exposure to pyridostigmine bromide, DEET, and/or permethrin causes sensorimotor deficit and alterations in brain acetylcholinesterase activity

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

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Military personnel deployed in the Persian Gulf War (PGW) were exposed to a combination of chemicals, including pyridostigmine bromide (PB), DEET, and permethrin. We investigated the dose-response effects of these chemicals, alone or in combination, on the sensorimotor performance and cholinergic system of male Sprague-Dawley rats. Animals were treated with a daily dermal dose of DEET and/or permethrin for 60 days and/or PB (gavage) during the last 15 days. Neurobehavioral performance was assessed on day 60 following the beginning of the treatment with DEET and permethrin. The rats were sacrificed 24 h after the last treatment for biochemical evaluations. PB alone, or in combination with DEET, or DEET and permethrin resulted in deficits in beam-walk score and longer beam-walk times compared to controls. PB alone, or in combination with DEET, permethrin, or DEET and permethrin caused impairment in incline plane performance and forepaw grip strength. PB alone at all doses slightly inhibited plasma butyrylcholinesterase activity, whereas combination of PB with DEET or permethrin increased its activity. Brainstem acetylcholinesterase (AChE) activity significantly increased following treatment with combinations of either DEET or permethrin at all doses, whereas the cerebellum showed a significant increase in AChE activity following treatment with a combination of PB/DEET/permethrin. Co-exposure to PB, DEET, and permethrin resulted in significant inhibition in AChE in midbrain. PB alone or in combination with DEET and permethrin at all doses increased ligand binding for m2 muscarinic acetylcholine receptor in the cortex. In addition, PB and DEET together or a combination of PB, DEET, and permethrin significantly increased ligand binding for nicotinic acetylcholine receptor. These results suggest that exposure to various doses of PB, alone and in combination with DEET and permethrin, leads to sensorimotor deficits and differential alterations of the cholinergic system in the CNS.

Original languageEnglish
Pages (from-to)253-262
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume77
Issue number2
DOIs
StatePublished - Feb 2004

Bibliographical note

Funding Information:
This study was supported, in part, by the U.S. Army Medical and Materiel Command under contract project order DAMD 17-99-1-9020.

Funding

This study was supported, in part, by the U.S. Army Medical and Materiel Command under contract project order DAMD 17-99-1-9020.

FundersFunder number
U.S. Army Materiel CommandDAMD 17-99-1-9020

    Keywords

    • Acetylcholinesterase
    • Brain
    • Butyrylcholinesterase
    • Combined exposure
    • DEET
    • M2 muscarinic acetylcholine receptor
    • Nicotinic acetylcholine receptor
    • Permethrin
    • Persian Gulf War
    • Pyridostigmine bromide
    • Sensorimotor

    ASJC Scopus subject areas

    • Biochemistry
    • Toxicology
    • Pharmacology
    • Clinical Biochemistry
    • Biological Psychiatry
    • Behavioral Neuroscience

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