Anxiety-like behavior in female mice changes by feeding, possible effect of guanylate cyclase C

Anxiety disorders are the most frequent mental disorders and are more prevalent in the female population. Up to date, an involvement of guanylate cyclase A and B in anxiety-like behavior has been suggested. In this study, we showed an expression of guanylate cyclase C (GC-C) in the amygdala which is regulated by feeding. Therefore, we further investigated sex differences of GC-C effects on anxiety levels with special attention to female estrous cycle and feeding. The effects of estrous cycle and feeding were investigated by several behavior tests: elevated plus maze, home cage escape and novelty-induced hypophagy. Possible changes in GC-C expression in amygdala and hypothalamus during estrous cycle were established by qPCR. When GC-C is activated (after a meal), the sex difference in all behavior tests used was abolished. As the expression of mRNA for GC-C in the amygdala increases 2 hr after a meal only in female animals, the anxiety levels change after a meal again only in female animals. When the anxiety levels are investigated, it is very important to pay attention not only to estrous cycle in female animals but also when animals were fed compared to the time point of the experiments. Concluding from our results, the sex differences in the incidence of anxiety disorders in humans could be GC-C dependent.