title: Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus.
abstract: The ability of alcohol to activate the hypothalamic-pituitary-adrenal (HPA) axis is well documented in investigations based in acute and short-term experimental paradigms. Herein, we have addressed the possibility that the prolonged exposure to ethanol concentrations that are initially effective in stimulating corticosteroid secretion might induce alterations in the response of the HPA axis that cannot be evinced by shorter exposures. Using conventional histological techniques, immunohistochemistry and in situ hybridization, we have examined the medial parvocellular division of the paraventricular nucleus (PVNmp), and the synthesis and expression of corticotropin-releasing hormone (CRH) and vasopressin (VP) by its constituent neurons, in rats submitted to 6 months of ethanol treatment and to withdrawal (2 months after 6 months of alcohol intake). Ethanol treatment and withdrawal did not produce neuronal loss in the PVNmp. However, the total number of CRH- and VP-immunoreactive neurons and the CRH mRNA levels were significantly decreased by ethanol treatment. In withdrawn rats, the number of CRH- and VP-immunostained neurons and the gene expression of CRH were increased relative to ethanol-treated rats and did not differ from those of controls. No significant variations were detected in VP mRNA levels as a result of ethanol treatment or withdrawal. These results show that prolonged alcohol intake blunts the expression of CRH and VP in the parvocellular neurons of the PVN, and that this effect is, partially at least, reversible by withdrawal. They also suggest that the development of tolerance to the effects of ethanol involve changes that take place at the hypothalamic level.
authors.affiliation: Department of Anatomy, Porto Medical School, Alameda Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Silva
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Paula-Barbosa
authors.forename: M Dulce
authors.initials: MD
authors.lastname: Madeira
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000437:Alcoholism / Q000235:genetics / Q000473:pathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014667:Vasopressins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D014667:Vasopressins; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone