Pattij Tommy, Groenink Lucianne, Hijzen Theo H, Oosting Ronald S, Maes Robert A A, van der Gugten Jan, Olivier Berend
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Neuropsychopharmacology. 2002 Sep;27(3):380-90. doi: 10.1016/S0893-133X(02)00317-2.
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.
5-羟色胺(1A)受体基因敲除(KO)小鼠在各种焦虑范式中表现出更焦虑的状态。由于焦虑通常与诸如体温升高和心动过速等自主神经变化相关,因此采用无线电遥测技术在应激/焦虑相关范式中研究野生型(WT)和基因敲除小鼠的这些参数。适应良好的野生型和基因敲除小鼠之间的基础体温(BT)、心率(HR)及其昼夜节律并无差异。在一项简单的应激测试即应激诱导体温过高(SIH)中,注射应激在基因敲除小鼠中导致了过度的应激反应。此外,5-羟色胺(1A)受体激动剂氟司必林在野生型小鼠中可剂量依赖性地拮抗应激诱导体温过高和应激诱导的心动过速,但在基因敲除小鼠中则不然。在两种基因型小鼠中,地西泮均可阻断应激诱导体温过高,但不能阻断应激诱导的心动过速。最后,基因敲除小鼠在心率和体温方面对新异应激表现出过度的应激反应;行为学上焦虑增强的迹象也支持了这一点。目前的研究结果表明,5-羟色胺(1A)受体基因敲除小鼠不仅在行为水平,而且在自主神经水平上均表现出更“类焦虑”的表型。