title: Temazepam triggers the release of vasopressin into the rat hypothalamic paraventricular nucleus: novel insight into benzodiazepine action on hypothalamic-pituitary-adrenocortical system activity during stress.
abstract: We investigated the influence of a representative classical benzodiazepine on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis activity both under basal conditions and stress. Adult male Wistar rats were intravenously administered with temazepam (0.5, 1, and 3 mg/kg body weight) and plasma concentrations of corticotropin (ACTH) and vasopressin (AVP) were measured in blood samples collected via chronically implanted jugular venous catheters. Simultaneously, the release of AVP within the hypothalamic paraventricular nucleus (PVN) was monitored via microdialysis. Plasma AVP levels remained unaffected by the different treatment conditions. Temazepam blunted the stressor exposure-induced secretion of ACTH in a dose-dependent manner. Concurrently, and also in a dose-dependent manner temazepam enhanced the intra-PVN release of AVP, known to originate from magnocellular neurons of the hypothalamic neurohypophyseal system. Furthermore, temazepam did not affect the in vitro secretion of ACTH from the adenohypophyseal cells. Taken together, the results of this study suggest that temazepam modulates the central nervous regulation of the HPA axis by altering intra-PVN AVP release. An increasingly released AVP of magnocellular origin seems to provide a negative tonus on ACTH secretion most probably via inhibiting the release of ACTH secretagogues from the median eminence into hypophyseal portal blood.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welt
authors.forename: Mario
authors.initials: M
authors.lastname: Engelmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Renner
authors.forename: Angelika
authors.initials: A
authors.lastname: Erhardt
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Martin E
authors.initials: ME
authors.lastname: Keck
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D017551:Microdialysis; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D010902:Pituitary Gland / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013693:Temazepam / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D018757:GABA Modulators; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D013693:Temazepam