title: Properly timed exposure to central ANG II prevents behavioral sensitization and changes in angiotensin receptor expression.
abstract: Previous studies show that the angiotensin type 1 receptor (AT1R) is susceptible to rapid desensitization, but that more chronic treatments that stimulate ANG II lead to sensitization of several responses. It is unclear, however, if the processes of desensitization and sensitization interact. To test for differences in AT1R expression associated with single or repeated injections of ANG II, we measured AT1R mRNA in nuclei that control fluid intake of rats given ANG II either in a single injection or divided into three injections spaced 20 min apart. Rats given a single injection of ANG II had more AT1R mRNA in the subfornical organ (SFO) and the periventricular tissue surrounding the anteroventral third ventricle (AV3V) than did controls. The effect was not observed, however, when the same cumulative dose of ANG II was divided into multiple injections. Behavioral tests found that single daily injections of ANG II sensitized the dipsogenic response to ANG II, but a daily regimen of four injections did not cause sensitization. Analysis of (125)I-Sar(1)-ANG II binding revealed a paradoxical decrease in binding in the caudal AV3V and dorsal median preoptic nucleus after 5 days of single daily injections of ANG II; however, this effect was absent in rats treated for 5 days with four daily ANG II injections. Taken together, these data suggest that a desensitizing treatment regimen prevents behavior- and receptor-level effects of repeated daily ANG II.
authors.affiliation: Department of Psychology, University at Buffalo, State University of New York (SUNY), Buffalo, New York;
authors.forename: Jessica
authors.initials: J
authors.lastname: Santollo
authors.affiliation: Department of Psychology, University at Buffalo, State University of New York (SUNY), Buffalo, New York;
authors.forename: Philip E
authors.initials: PE
authors.lastname: Whalen
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida; Department of Pharmacology and Physiology, College of Medicine, Georgetown University, Washington, DC; and.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, SUNY, Buffalo, New York.
authors.forename: Stewart D
authors.initials: SD
authors.lastname: Clark
authors.affiliation: Department of Psychology, University at Buffalo, State University of New York (SUNY), Buffalo, New York; danielsd@buffalo.edu.
authors.forename: Derek
authors.initials: D
authors.lastname: Daniels
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D004326:Drinking / Q000187:drug effects*; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
keywords: AT1R; drinking microstructure; fluid balance; water intake