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Pharmacological manipulation of immune-induced food aversion in rats
Eduardo C Zarzana1, Alexandre S Basso, Frederico A Costa-Pinto
1Laboratory of Pharmacology and Toxicology, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil.
Background:
Mice allergic to ovalbumin (OVA) avoid drinking a solution containing this antigen. This was interpreted as related to IgE-dependent mast cell degranulation and sensory C fiber activation.
Methods:
We employed pharmacological manipulation to further investigate the mediators involved in immune-induced food aversion.
Results:
While nonimmunized rats preferred a sweetened OVA solution, immunized rats avoided it. We also employed a paradigm in which rats are conditioned to drink water for two 10-min sessions a day. Tolerant rats presented lower IgE titers, and this manipulation abrogated food aversion. Dexamethasone (1.0 mg/kg) prevented the aversion of OVA-immunized rats to the antigen-containing solution. Combined blockade of H(1) and 5-hydroxytryptamine (5-HT)(2) receptors by promethazine (3.0 mg/kg) plus methysergide (5.0 mg/kg) was unable to alter food aversion. Blockade of 5-HT(3) receptors by ondansetron (1.0 mg/kg) caused a twofold increase in the ingestion of the sweetened OVA solution by immunized rats, suggesting the involvement of 5-HT(3) receptors in food aversion. Finally, we showed that dexamethasone or promethazine plus methysergide, but not ondansetron, effectively prevented the IgE-dependent mast-cell-degranulation-induced increase in vascular permeability in rats.
Conclusion:
We suggest that regardless of whether or not they cause edema, IgE-mediated mast cell degranulation and consequent 5-HT(3) signaling are involved in the process that triggers avoidance to the source of the allergen in allergic rats.
