Central administration of pmol and low nmol doses of neurotensin (NT), rapidly stimulated hypothalamic-pituitary adrenal (HPA) activity, increasing adrenocorticotropin hormone (ACTH) and corticosterone (B) release for several hours. This suggests potent effects of centrally administered NT and a role for this neuropeptide in HPA regulation. Of several brain areas thought to be involved in mediating NT-induced effects, one site of particular interest is the paraventricular nucleus of the hypothalamus (PVNh). Chronic implants of the NT antagonist, SR 48692 (powdered form), into the PVNh area decreased HPA activity under both basal and stress-induced conditions. These findings suggest an endogenous role for NT in mediating hypophysiotropic HPA signalling. Decreases in immunoreactive (ir) corticotropin-releasing hormone (CRH) expression was also seen following chronic SR 48692 exposure (day 7). This decrease in irCRH levels paralleled the SR 48692-induced inhibition in ACTH and B release, suggesting that CRH is involved in mediating SR 48692-induced effects on HPA activity. / Chronic intracerebroventricular (icv) delivery of NT (1 pmol/h for 14 days) into the rat brain had an opposing effect than that of SR 48692. / Chronic NT treated animals demonstrated increased fear/anxiety-related behavior. Decreased mean locomotor activity was observed in the chronic NT-treated (1 pmol/h for 14 days) animals upon exposure to a novel environment. Thus, a NT-CRH mechanism of action appears to be involved in mediating behavioral responses to stress. In addition to a proposed role for CRH mediating NT-induced HPA regulation, it also appears to be mediating fear/anxiety-related behavior. / Finally, we examined the status of NT receptors in animals with known deficits in HPA function. Aged, 24 month old Long-Evans rats, were identified as either aged, cognitively impaired (AI) or aged, cognitively unimpaired (AU) compared to young adult control rats. The AI animal showed decreased levels of [125I]NT binding sites in areas such as CA3 (42%) and DG (55%) of the hippocampus and the PVNh (72%) compared to the young controls. The fact that this is occurring in the animal known to exhibit HPA hyperactivity lends further support for a NT role in regulating HPA function. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35481 |
| Date | January 1999 |
| Creators | Rowe, Wayne, 1961- |
| Contributors | Quirion, Remi (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650456, proquestno: NQ50250, Theses scanned by UMI/ProQuest. |
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