Role of opioid receptor like-1 receptor in modulation of endocrine, immunological, and behavioral responses to the T-cell superantigen staphylococcal enterotoxin A

Opioid receptor like-1 receptor (ORL1) is selective for orphaninFQ/nociceptin (OFQ/N), a peptide linked to stress. Since immunologic stimuli exert stressor-like effects, the neuroendocrine and behavioral effects of the T-cell superantigen staphylococcal enterotoxin A (SEA) were tested in ORL1−/− and ORL1+/+ wildtype 129S6 mice. Within 2 h of SEA challenge both genotypes showed elevated corticosterone, but only wildtypes were elevated after 4 h, and had altered hypothalamic CRH mRNA. Although amygdaloid CRH and TNFα mRNA was increased by SEA, this did not vary with genotype. Interestingly, gustatory neophobia due to SEA challenge was augmented in ORL1−/− mice, although object neophobia tested 4 days later was abrogated. These results suggest differential requirements for ORL1 in the mediation of neuroimmune effects exerted at different times after an immune challenge.