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ToxSci Advance Access originally published online on January 19, 2005
Toxicological Sciences 2005 84(2):360-367; doi:10.1093/toxsci/kfi092
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Toxicological Sciences vol. 84 no. 2 © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Neuroanatomical Targets of the Organophosphate Chlorpyrifos by c-fos Immunolabeling

F. Carvajal, M. C. Sánchez-Amate, F. Sánchez-Santed and I. Cubero1

Department of Neurociencia y Ciencias de la Salud, University of Almeria, 04120 Almeria, Spain

Received November 17, 2004; accepted January 18, 2005

Chlorpyrifos (CPF) is an organophosphate widely used as an insecticide in agriculture which elicits short- and long-term neurobehavioral deficits after acute administration. Because little is known about the specific brain areas targeted by CPF, investigating for the location of its neuroanatomical targets could help to describe the brain systems involved in the neurobehavioral toxicity developed in CPF-exposed organisms. To meet this objective, in the present study we evaluated CPF-induced c-fos expression. In addition, locomotor behavior and cerebral cholinesterase level were evaluated. We found two main sets of results. First, no significant c-fos expression was found in cholinoceptive regions in CPF-treated rats 2 h or 24 h post-administration, despite the fact that 41% and 62% acetylcholinesterase inhibition, respectively, were present in brain homogenates. These results are consistent with previous reports showing CPF-induced activation of adaptive neural mechanisms re-establishing cholinergic tone. Second, 24 h post-intoxication CPF elicited c-fos expression in cytokine-related areas. Cytokines have been involved in anxiety-like responses and psychiatric stress syndromes. Taking into account that CPF triggers the synthesis of peripheral cytokines, the present data stress the need to further clarify functional relations between organophosphate-triggered peripheral cytokines and emotional disturbances reported in intoxicated organisms.

Key Words: chlorpyrifos; cytokines; c-fos; lithium chloride; cholinonoceptive areas.


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