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ToxSci Advance Access published online on January 19, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi092
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Toxicological Sciences © Society of Toxicology 2005; all rights reserved.
Received November 17, 2004
Accepted November 18, 2005

Neurotoxicology

Neuroanatomical Targets of the Organophosphate Chlorpyrifos by c-fos immunolabeling

F. Carvajal 1, MC. Sánchez-Amate 1, F. Sánchez-Santed 1, and I. Cubero 1*

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

* To whom correspondence should be addressed.
I. Cubero, E-mail: icubero{at}ual.es


  Abstract

Chlorphyrifos (CPF) is an Organophosphate widely used as insecticide in agriculture (Pope, 1999, Richardson, 1995) which elicits short- and long-term neurobehavioral deficits after acute administration (Abou-Donia, 2003a; Richardson, 1995). Since 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 behaviour and cerebral cholinesterase level was evaluated. We found two main sets of results. First, no significant c-fos expression was found in cholinoceptive regions in CPF-treated rats 2h or 24h post-administration, despite the fact that 41% and 62% acetylcholinesterase inhibition were respectively present in brain homogenates. These results are consistent with previous reports showing CPF induced activation of adaptive neural mechanisms re-establishing cholinergic tone. Second, 24h post-intoxication CPF elicited c-fos expression in cytokine-related areas. Cytokines have been involved in anxiety-like responses and psychiatric stress syndromes (Anisman and Merali, 2003; Dantzer, 2001; Kronfol and Remick, 2000). Taking into account that CPF triggers the synthesis of peripheral cytokines the present data stress the need to further clarify functional relations between Organophosphates-triggered peripheral cytokines and emotional disturbances reported in intoxicated organisms.

Keywords: Chlorpyrifos; cytokines; c-fos; Lithium Chloride; Cholinonoceptive areas.
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