Prolonged Exposure to Intermittent Alcohol Vapors Blunts Hypothalamic Responsiveness to Immune and Non‐Immune Signals

• DOI: 10.1111/j.1530-0277.2000.tb04560.x
• Publication Date: 2006-05-30T13:40:13Z
• Authors: Soon Lee; Donné Schmidt; Fred Tilders; Maury Cole; Amanda Smith; Catherine Rivier
• Keywords: Lipopolysaccharides; Male; Hypothalamo-Hypophyseal System; Ethanol; Hypothalamus; Pituitary-Adrenal System; Endotoxemia; Rats; Rats, Sprague-Dawley; Alcoholism; 03 medical and health sciences; 0302 clinical medicine; Adrenocorticotropic Hormone; Microscopy, Fluorescence; Animals; Arousal; Paraventricular Hypothalamic Nucleus

Background: We have previously shown that long‐term alcohol treatment blunts the ACTH response to itself, as well other stresses, and is accompanied by decreased pituitary responsiveness vasopressin (VP), but not corticotropin‐releasing factor (CRF). The present work aims determine relevance of changes in CRF VP receptors gland and/or peptide stores neurons paraventricular nucleus (PVN) hypothalamus, areas are most directly involved release. Methods: Intact male rats were exposed using a new vapor delivery system which enables individual rat housing boxes. Alcohol was delivered for 6 hr once daily (0700‐1300), after returned their home cages where they had free access food water. Control kept similar boxes, alcohol. Total time 8 days. All animals equipped with indwelling jugular cannulae used monitor blood levels (BALs) corticosterone release throughout drug exposure. Due presence swivel, animals’movements restricted or hindered these cannulae. On morning day 9, decapitated under basal conditions neurogenic (mild electrofootshocks) systemic [iv lipopolysaccharide (LPS)] stimulus. PVN neuronal responses, indicated mRNA concentrations immediate early genes (IEGs) c‐ fos NGFI‐B, plasma measured before during endotoxemia electrofootshocks. Results: In absence alcohol, remained at levels, indicating environment‐induced stress. BALs consistent predictable, we targeted peak values about 200 mg%. At end period, there no significant differences between receptor anterior control alcohol‐treated rats. contrast, respectively increased external zone median eminence. It also NGFI‐B transcripts magnocellular (m) portion PVN, parvicellular (p) division this (i.e., shocks LPS). After exposure stressors, on hand, all groups showed increases up‐regulation response, pPVN IEGs transcripts. However, hormonal responses significantly blunted pretreated Conclusions: Collectively, our results suggest activation represents an important mechanism ability blunt endotoxemia. addition, developed practical reliable, has advantage it measurement circulating hormone animals.