Scholars@Duke publication: Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging.

Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging.

Publication , Journal Article

Levin, ED; Timofeeva, OA; Yang, L; Petro, A; Ryde, IT; Wrench, N; Seidler, FJ; Slotkin, TA

Published in: Behav Brain Res

April 2, 2010

Developmental exposure of rats to the organophosphate (OP) pesticides leads to altered neurobehavioral function in juvenile and young adult stages. The current study was conducted to determine whether effects of neonatal parathion exposure on cognitive performance persist in older adult and aged rats, and the relationship of behavioral changes to underlying cholinergic and serotonergic mechanisms. We administered parathion to rat pups on postnatal days 1-4, at doses spanning the threshold for the initial signs of systemic toxicity and for barely detectable cholinesterase inhibition (0.1 or 0.2 mg/kg/day). Beginning at 14 months of age and continuing until 19 months, the rats were trained in the 16-arm radial maze. Controls showed the normal sex difference in this spatial learning and memory task, with the males committing significantly fewer working memory errors than females. Neonatal parathion exposure eliminated the sex difference primarily by causing impairment in males. In association with the effects on cognitive performance, neonatal parathion exposure elicited widespread abnormalities in indices of serotonergic (5HT) and cholinergic synaptic function, characterized by upregulation of 5HT(2) receptors and the 5HT transporter, deficits in choline acetyltransferase activity and nicotinic cholinergic receptors, and increases in hemicholinium-3 binding to the presynaptic choline transporter. Within-animal correlations between behavior and neurochemistry indicated a specific correlation between working memory performance and hippocampal hemicholinium-3 binding; parathion exposure eliminated this relationship. Like the behavioral effects, males showed greater effects of parathion on neurochemical parameters. This study demonstrates the sex-selective, long-term behavioral alterations caused by otherwise nontoxic neonatal exposure to parathion, with effects increasingly expressed with aging.

Duke Scholars

Author Edward Daniel Levin Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...

Author Frederic J. Seidler Pharmacology & Cancer Biology

Author Theodore Alan Slotkin Pharmacology & Cancer Biology

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Published In

Behav Brain Res

DOI

10.1016/j.bbr.2009.11.007

EISSN

1872-7549

Publication Date

April 2, 2010

Volume

208

Issue

Start / End Page

319 / 327

Location

Netherlands

Related Subject Headings

Sex Preselection
Serotonin
Receptors, Nicotinic
Rats, Sprague-Dawley
Rats
Protein Binding
Pregnancy
Parathion
Neurotransmitter Uptake Inhibitors
Neurology & Neurosurgery

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Chicago

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Levin, E. D., Timofeeva, O. A., Yang, L., Petro, A., Ryde, I. T., Wrench, N., … Slotkin, T. A. (2010). Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav Brain Res, 208(2), 319–327. https://doi.org/10.1016/j.bbr.2009.11.007

Levin, Edward D., Olga A. Timofeeva, Liwei Yang, Ann Petro, Ian T. Ryde, Nicola Wrench, Frederic J. Seidler, and Theodore A. Slotkin. “Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging.” Behav Brain Res 208, no. 2 (April 2, 2010): 319–27. https://doi.org/10.1016/j.bbr.2009.11.007.

Levin ED, Timofeeva OA, Yang L, Petro A, Ryde IT, Wrench N, et al. Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav Brain Res. 2010 Apr 2;208(2):319–27.

Levin, Edward D., et al. “Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging.” Behav Brain Res, vol. 208, no. 2, Apr. 2010, pp. 319–27. Pubmed, doi:10.1016/j.bbr.2009.11.007.

Levin ED, Timofeeva OA, Yang L, Petro A, Ryde IT, Wrench N, Seidler FJ, Slotkin TA. Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav Brain Res. 2010 Apr 2;208(2):319–327.