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ToxSci Advance Access published online on February 13, 2006
Toxicological Sciences, 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
Received November 18, 2005
Accepted February 2, 2006

Neurotoxicology

Lateral Parabrachial lesions disrupt Paraoxon-induced conditioned flavor avoidance

M. López-Grancha 1, M. C. Sánchez-Amate 1, M. Navarro 2, F. Carvajal 1, F. Sánchez-Santed 1, and I. Cubero 1 *

1 Departamento de Neurociencia y Ciencias de la Salud, University of Almeria, Almeria, Spain
2 Bowles Center for Alcohol Studies, Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, USA

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


  Abstract

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering Multiple Chemical Sensitivity (MCS) 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 analyzing the involvement of conditioning in sickness-syndromes potentially linked to OP poisoning. The first objective in the present study addressed if Paraoxon (PX), the neuroactive metabolite of the organophosphate 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 aimed to characterize the nature of the specific physiological cue serving as unconditioned stimulus in PX-induced conditioned avoidance. Despite PX-administration triggered 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 stimulus 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 is discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness-syndromes potentially induced by OP exposure.

Keywords: Paraoxon; Organophosphates; associative sickness-properties; conditioned flavor aversion; lateral parabrachial area.
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