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ToxSci Advance Access originally published online on February 13, 2006
Toxicological Sciences 2006 91(1):210-217; doi:10.1093/toxsci/kfj126
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Lateral Parabrachial Lesions Disrupt Paraoxon-Induced Conditioned Flavor Avoidance

Matilde López-Grancha*, Carmen Sánchez-Amate*, Montserrat Navarro{dagger}, Francisca Carvajal*, Fernando Sánchez-Santed* and Inmaculada Cubero*,1

* Departamento de Neurociencia y Ciencias de la Salud, University of Almeria, 04120 Almeria, Spain; and {dagger} Bowles Center for Alcohol Studies, Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599

Received November 18, 2005; accepted February 2, 2006

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimului supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.

Key Words: paraoxon; organophosphates; associative sickness properties; conditioned flavor aversion; lateral parabrachial area.


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