Allergic rhinitis induces anxiety-like behavior and altered social interaction in rodents

Epidemiological and clinical studies report higher incidences of anxiety and increased emotional reactivity in individuals suffering from respiratory allergies. To evaluate if respiratory allergies are capable of promoting anxiety-like behavior in rodents, we used models of allergic rhinitis and behavioral evaluations followed by assessment of mRNA for cytokines in relevant brain regions. Mice and rats were sensitized to ovoalbumin or pollen, respectively, following standard sensitization and challenge protocols. After challenge, the animals were evaluated in the open field, elevated plus-maze and resident-intruder tests. Cytokines and corticotropin-releasing factor expression were assessed in several brain regions by real-time RT-PCR and plasma corticosterone concentrations by radioimmunoassay. Mice and rats sensitized and exposed to allergen showed increased anxiety-like behavior and reduced social interaction without any overt behavioral signs of sickness. T-helper type 2 (T(H)2) cytokines were induced in both rats and mice in the olfactory bulbs and prefrontal cortex and remained unchanged in the temporal cortex and hypothalamus. The same results were found for CRF mRNA expression. No differences were observed in corticosterone concentrations 1h after the last behavioral test. These results show that sensitization and challenge with allergens induce anxiety across rodent species and that these effects were paralleled by an increased expression of T(H)2 cytokines and CRF in the prefrontal cortex. These studies provide experimental evidence that sensitized rodents experience neuroimmune-mediated anxiety and reduced social interaction associated with allergic rhinitis.