title: Autonomic changes associated with enhanced anxiety in 5-HT(1A) receptor knockout mice.
abstract: 5-HT(1A) receptor knockout (KO) mice have been described as more anxious in various anxiety paradigms. Because anxiety is often associated with autonomic changes like elevated body temperature and tachycardia, radiotelemetry was used to study these parameters in wild type (WT) and KO mice in stress-/anxiety-related paradigms. Basal body temperature (BT), heart rate (HR), and their diurnal rhythmicity did not differ between well-adapted WT and KO mice. In a simple stress-test, the Stress-induced Hyperthermia (SIH), injection-stress resulted in an exaggerated stress-response in KO mice. Furthermore, the 5-HT(1A) receptor agonist flesinoxan dose-dependently antagonized SIH and stress-induced tachycardia in WT, but not in KO, mice. In both genotypes, diazepam blocked SIH, but not stress-induced tachycardia. Finally, KO mice displayed an exaggerated stress response in HR and BT to novelty stress; this was supported by behavioral indications of enhanced anxiety. The present findings show that 5-HT(1A) receptor KO mice display a more "anxious-like" phenotype not only at a behavioral, but also at autonomic levels.
authors.affiliation: Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. t.pattij@pharm.uu.nl
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Theo H
authors.initials: TH
authors.lastname: Hijzen
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
authors.forename: Robert A A
authors.initials: RA
authors.lastname: Maes
authors.forename: Jan
authors.initials: J
authors.lastname: van der Gugten
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D013312:Stress, Physiological
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C056895:flesinoxan; D003975:Diazepam