Pharmacological Manipulation of Immune-Induced Food Aversion in Rats

Abstract

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 H₁ 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-HT₃ 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-HT₃ 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-HT₃ signaling are involved in the process that triggers avoidance to the source of the allergen in allergic rats.

Neural Pathways in Allergic Inflammation

“…The pre-treatment with a glucocorticoid (dexamethasone) inhibited both intestinal edema and food aversion [32]. Similar results were observed in rats [49]. This data suggests that the pharmacological effects of histamine or serotonin are not essential to the development of immunological food aversion.…”

“…In this vein, neonatal treatment with capsaicin, a neurotoxin derived from chilli pepper (plants from the genus Capsicum ) that promotes a selective dysfunction of sensory fibers such as C-fibers [61], completely blocked c- fos expression in the PVN [36] and diminished food aversion in OVA-sensitized mice [62]. The treatment with antagonist of 5-HT3 receptors, expressed in sensory C-fibers [63], diminished the expression of food aversion behavior in sensitized rats [49]. Altogether, these results corroborate the hypothesis that mediators released by mast cell degranulation could stimulate the nerve endings of the C-fibers that, in turn, would transmit the sensory information to the CNS.…”

Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic consequences induced by experimental food allergy

“…As well as being a key event during anaphylactic shock, mast cell activation has an important role in allergen aversion by sensitized mice. It was shown that this process happens through IgE-mediated mast cell degranulation * with consequent 5-HT3 signalling [28]. It has also been shown that this aversion is immune-based [29] and is dependent upon both IgE [20] and IL-4 [18].…”

Allergic host defences

“…This aversion was allergen-specific and dependent on the immune system 79 . Furthermore, available evidence suggests that allergen-containing food aversion is dependent on functional C-fiber innervation 80, 81 . Interestingly, allergen sensitized mice exhibited increased level of anxiety upon exposure to the allergen, consistent with avoidance of allergen- containing environment.…”