Groenink L, van Bogaert M J V, van der Gugten J, Oosting R S, Olivier B
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Behav Pharmacol. 2003 Sep;14(5-6):369-83. doi: 10.1097/01.fbp.0000087737.21047.75.
Generation of receptor knockout mice has offered a new approach to study processes underlying anxiety. In this paper, studies focusing on anxiety using 5-HT1A receptor knockout (1AKO) and 5-HT1B receptor knockout (1BKO) mice are reviewed. 1AKO mice on different genetic background strains have initially been described as more anxious. In 1AKO mice on the 129/Sv background strain, the initial findings could not always be replicated, although under certain conditions, mild anxiety-like responses were observed in these 1AKO mice. In 1BKO mice, some indications of reduced anxiety have been found, but these observations may be confounded partly with increased motor impulsivity of these mutants. To study whether the putative effects of the null mutations on anxiety were reflected in the autonomic nervous system, basal heart rate and body temperature of 1AKO and 1BKO mice were measured, as well as their autonomic responses to novel cage exposure and to reversal of the light-dark rhythm. 1AKO mice did not differ from wild-type mice in any parameter, neither under non-stress conditions, nor following novel cage exposure. In 1BKO mice, basal heart rate was reduced and body temperature was increased. 1BKO mice showed exaggerated autonomic responses to novel cage stress. Adaptation to the reversal of the light-dark cycle was comparable in the three genotypes. The stress-induced hyperthermia procedure showed no differential responses of the three genotypes to the stressor. Pharmacological responses to various psychotropic drugs in the stress-induced hyperthermia test were also comparable in 1AKO, 1BKO and wild-type mice. The present data illustrate the complexity of studying the behavioural and physiological consequences of deletion of genes coding for important receptors in the CNS.
受体基因敲除小鼠的产生为研究焦虑潜在机制提供了一种新方法。本文综述了利用5-羟色胺1A受体基因敲除（1AKO）和5-羟色胺1B受体基因敲除（1BKO）小鼠对焦虑进行的研究。最初，不同遗传背景品系的1AKO小鼠被描述为更焦虑。在129/Sv背景品系的1AKO小鼠中，最初的研究结果并非总能重复，尽管在某些条件下，这些1AKO小鼠表现出轻度焦虑样反应。在1BKO小鼠中，发现了一些焦虑减轻的迹象，但这些观察结果可能部分与这些突变体运动冲动性增加有关。为了研究无效突变对焦虑的假定影响是否反映在自主神经系统中，测量了1AKO和1BKO小鼠的基础心率和体温，以及它们对新笼环境暴露和昼夜节律颠倒的自主反应。1AKO小鼠在任何参数上与野生型小鼠均无差异，无论是在非应激条件下，还是在新笼环境暴露后。在1BKO小鼠中，基础心率降低，体温升高。1BKO小鼠对新笼应激表现出过度的自主反应。三种基因型对昼夜节律颠倒的适应情况相当。应激诱导的体温过高实验显示，三种基因型对应激源的反应没有差异。在应激诱导的体温过高实验中，1AKO、1BKO和野生型小鼠对各种精神药物的药理反应也相当。目前的数据说明了研究中枢神经系统中重要受体编码基因缺失的行为和生理后果的复杂性。
