Effects of staphylococcal enterotoxin A on pituitary-adrenal activation and neophobic behavior in the C57BL/6 mouse.

Bacterial superantigens, such as the staphylococcal enterotoxins (SE), exert a strong capacity for in vivo stimulation of T cell proliferation and cytokine production. Among these superantigens, staphylococcal enterotoxin B (SEB) has been shown to promote anxiety-like properties, possibly mediated by activation of central corticotropin-releasing hormone. In the present study, using male C57BL/6J mice, it was shown that challenge with another prominent superantigen, staphylococcal enterotoxin A (SEA), produced a dose-dependent (0.2-50 microg/mouse) increase in corticosterone and ACTH levels. Interestingly, while the adrenocorticoid response to SEA persisted in cyclosporine A-pretreated mice, it was completely abolished in RAG-1 deficient mice that lack functional T and B lymphocytes. The latter is consistent with the need for cellular interactions involving T cells and B cells (probably in an antigen-presenting capacity) that will initiate events leading to pituitary-adrenal activation by SEA. Since pituitary-adrenal activation typically alters "emotional" reactivity in animals, a final set of experiments assessed behavioral responses to an open field, exposure to a novel object, and a novel appetitive stimulus. These tests revealed a significant augmentation of reactivity to the novel object in SEA-challenged mice, although activity in the open field was not affected. Furthermore, consumption of a novel solution was reduced only if testing involved unfamiliar contextual circumstances. This suggested that anorexic effects per se were not induced by SEA at the dose used, but that attentional mechanisms focused on novelty were enhanced.