Posted by davpet on May 28, 2003, at 12:28:41
In reply to Re: Naltrexone and the HPA axis : Mechanism of Action » davpet, posted by MB on May 27, 2003, at 23:16:26
It is my understanding that it would , if the theory holds , as it would sensitise the HPA axis. The way i look at it is the HPA axis is a good thing its our bodies way of dealing with stress , however it must be working effectively turn ON when stress is applied and then turn OFF effectively through negative feedback inhibition. If there is a problem somewhere along the line it will manifest itself through various symptoms .
Article which tou might find interesting :
Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function
Ivar Dijkstra1, Fred J. H. Tilders1, Greti Aguilera2, Alexander Kiss2, Cristina Rabadan-Diehl2, Nicholas Barden3, Sharada Karanth4, Florian Holsboer4, and Johannes M. H. M. Reul4
1 Graduate School Neurosciences Amsterdam, Department of Pharmacology, Research Institute Neurosciences Vrije Universiteit, 1081 BT Amsterdam, The Netherlands, 2 Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, 3 Neuroscience, Centre Hospitalier de l'Université Research Centre and Department of Physiology, Laval University, Québec, Canada G1V 4G2, and 4 Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Section Neuroimmunoendocrinology, D-80804 Munich, GermanyLoss of central glucocorticoid receptor (GR) function is thought to be involved in the development of neuroendocrine and psychiatric disorders associated with corticotropin-releasing hormone (CRH) hyperactivity. The possible causal relationship between defective GR function and altered activity of CRH neurons was studied in transgenic mice (TG) expressing antisense RNA against GR. Immunocytochemical studies showed significant reductions in CRH immunoreactive neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP) stores in the external zone of the median eminence. Concomitantly, stimulus-evoked CRH secretion from mediobasal hypothalami of TG mice in vitro was reduced significantly. However, CRH mRNA levels in the PVN of TG mice were marginally lower than those in wild-type (WT) mice. 125I-CRH binding autoradiography revealed no differences between WT and TG animals in any of the brain regions that were studied. Basal plasma corticosterone (cort) levels and 125I-CRH binding, CRH-R1 mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary gland were similar in WT and TG mice. Intraperitoneal injection of interleukin-1 (IL-1) increased plasma cort levels, CRH mRNA in the PVN, and anterior pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline significantly reduced anterior pituitary CRH-R1 mRNA levels in WT mice, but not in TG mice, whereas IL-1 produced a decrease in these mRNA levels in both strains.
The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R1 mRNA to stimulus-induced downregulation. Moreover, the hypothalamic changes observed in this model suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.
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