title: GABAA-benzodiazepine receptor complex ligands and stress-induced hyperthermia in singly housed mice.
abstract: Stress-induced hyperthermia (SIH) in singly housed mice, in which the rectal temperature of a mouse is measured twice with a 10-min interval, enables to study the effects of a drug on the basal (T1) and on the stress-enhanced temperature (T2), 10 min later, using the rectal procedure as stressor. SIH (T2-T1) reflects a stress-induced phenomenon sensitive to stress- or anxiety-modifying effects of drugs. Several benzodiazepine agonists (diazepam, chlordiazepoxide, oxazepam and alprazolam) dose-dependently antagonized SIH either in NMRI mice from two different breeders or in BALB/c mice. No major differences in the sensitivity for any of the drugs tested were found between strains or between substrains from different breeders. The selective BZ1 receptor agonists alpidem and zolpidem only at relatively high doses antagonized SIH, whereas flumazenil, FG7142, pentylenetetrazol and phenobarbital did not affect SIH. Alcohol antagonized SIH, and the effects of diazepam could be antagonized by flumazenil. The findings that full BZ receptor agonists have anxiolytic-like effects in the singly housed SIH paradigm are comparable to those previously found in the group-housed version. The singly housed SIH is proposed as a simple and reliable screen for detecting anxiety-like properties of drugs that is valid in every mouse strain tested so far.
authors.affiliation: Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands. b.olivier@pharm.uu.nl
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: J Adriaan
authors.initials: JA
authors.lastname: Bouwknecht
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
authors.forename: Christina
authors.initials: C
authors.lastname: Leahy
authors.forename: Ruud
authors.initials: R
authors.lastname: van Oorschot
authors.forename: Theo J J
authors.initials: TJ
authors.lastname: Zethof
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000188:drug therapy / Q000503:physiopathology; D058785:GABA-A Receptor Agonists; D006799:Housing, Animal; D008024:Ligands; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000502:physiology; D013312:Stress, Physiological / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D058785:GABA-A Receptor Agonists; D008024:Ligands; D011963:Receptors, GABA-A; D003975:Diazepam