Autonomic changes associated with enhanced anxiety in 5-HT(1A) receptor knockout mice.
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.
Pattij
Tommy
T
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. t.pattij@pharm.uu.nl
Groenink
Lucianne
L
Hijzen
Theo H
TH
Oosting
Ronald S
RS
Maes
Robert A A
RA
van der Gugten
Jan
J
Olivier
Berend
B
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
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C056895:flesinoxan; D003975:Diazepam