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To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine\u2010dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c\u2010Fos induction and heteronuclear (hn)RNA levels of corticotropin\u2010releasing hormone (CRH) and arginine vasopressin (AVP) in na\u00efve and morphine dependent animals injected with saline or 5\u2003mg\/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2\u2003h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Na\u00efve rats and animals that were implanted with morphine pellets for 8\u2003days did not display significant up\u2010regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic\u2010related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04421.x","type":"journal-article","created":{"date-parts":[[2007,2,5]],"date-time":"2007-02-05T12:43:30Z","timestamp":1170679410000},"page":"1060-1071","source":"Crossref","is-referenced-by-count":53,"title":["Activation of stress\u2010related hypothalamic neuropeptide gene expression during morphine withdrawal"],"prefix":"10.1111","volume":"101","author":[{"given":"Cristina","family":"Nunez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"F\u00f6ldes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Luisa","family":"Laorden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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