Cholinergic hypersensitivity in intestinal allergy and depression

Experimental evidence suggests that an enhanced cholinergic state may increase host susceptibility to allergies as well as to stress-induced depression; and hypersensitivity to cholinergic agonists has been reported both in allergic and depressive patients. The objective of this study was to investigate whether genetically heightened cholinergic responsiveness may be a trait predisposing its carriers to both allergies and depression. In a series of experiments, we compared two hypercholinergic rat strains, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL), both genetically predisposed to stress-induced depression, with their control counterparts, Wistar rats and Flinders Resistant Line rats, respectively, for their susceptibility to immediate hypersensitivity reactions. Following sensitization to ovalbumin (OA), rats were challenged by ip injection with 3 mg OA or saline. In spite of negative findings of line- or strain-related difference in IgE titres, FSL and WKY rats were more susceptible to immediate hypersensitivity relative to the controls. This was evidenced by more pronounced mast cell degranulation, and more intense systemic and peripheral (intestinal) allergic reactions. In an additional experiment, we showed that in vivo pretreatment with cholinergic agonists exacerbated intestinal antigen-induced reactions, again indicating cholinergic involvement. Our data provide further evidence for a common cholinergic mechanism in susceptibility to both allergies and depression. The present findings are also compatible with empirical studies reporting prevalence of atopic disorders in people with depression