TitleOpioid receptor like-1 receptor deficient mice show dysregulation of the hypothalamic pituitary adrenal axis following acute immunologic challenge with staphylococcal enterotoxin A
NameMallimo, Elyse M. (author), Kusnecov, Alexander (chair), Shors, Tracey (internal member), Wagner, George (internal member), Rutgers University, Graduate School - New Brunswick,
Stress (Physiology)--Endocrine aspect
DescriptionOpioid receptor like-1 receptor (ORL1) shares considerable sequence identity with the classical µ, δ, and κ opioid receptors yet shows no affinity to the classical opioid ligands. Rather, ORL1 is selective for its endogenous ligand, orphaninFQ/Nociceptin (OFQ/N). The nociceptin system is integral to many physiological processes (e.g., nociception) and plays a prominent role in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, the stress response, and anxiety. Since immunologic stimuli exert stressor-like effects, the neuroendocrine and behavioral effects of the T-cell superantigen staphylococcal enterotoxin A (SEA) were tested in 129S6, ORL1 wildtype (ORL1+/+) and knockout (ORL1-/-) mice. Within 2 h of SEA challenge both genotypes showed elevated levels of plasma corticosterone, but only wildtypes remained elevated after 4 h. The effects of SEA on corticosterone levels were determined to be associated with changes in corticotropin releasing hormone (CRH), CRH receptor 1 (CRH-R1) and CRH-R2 mRNA expression in the hypothalamus. Moreover, SEA-induced changes in CRH and CRH-R1 were dependent on the presence of the ORL1 gene and suggest that activation of the ORL1 receptor may modulate positive and negative feedback control of CRH activity in the hypothalamus. These findings are consistent with the idea that ORL1 activation prolongs stress-induced levels of corticosterone, possibly through ORL1 dependent modulation of the CRH system. Furthermore, gustatory neophobia due to SEA challenge was augmented in ORL1-/- mice and is consistent with the anxiolytic role for the nociceptin system. In summary, these results suggest that the ORL1 gene may be necessary for normal HPA axis activity and may confer resistance to novelty-induced anorexia following acute SEA challenge in 129S6 mice.
NoteIncludes bibliographical references
Noteby Elyse M Mallimo
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.