Liebsch G, Landgraf R, Gerstberger R, Probst J C, Wotjak C T, Engelmann M, Holsboer F, Montkowski A
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Regul Pept. 1995 Oct 20;59(2):229-39. doi: 10.1016/0167-0115(95)00099-w.
We studied the role of central amygdala CRH receptors in behavioral responses to an anxiogenic stimulus. An antisense oligodeoxynucleotide corresponding to the rat CRH1 receptor mRNA was infused chronically into the central amygdaloid nucleus of male rats via osmotic minipumps (0.25 micrograms/0.5 microliters/h). Control groups received infusions of either a scrambled sequence oligodeoxynucleotide or vehicle. On the 4th day of treatment, rats were subjected to 10 min of social defeat and immediately afterwards tested on the elevated plus-maze. Antisense oligodeoxynucleotide-treated rats spent significantly more time exploring the open arms of the plus-maze than scrambled sequence- and vehicle-treated animals, both of which did not differ from each other. The social discrimination test, on the other hand, revealed no difference in juvenile recognition abilities among the treatment groups. Using in situ hybridization and receptor autoradiography, we were not able to detect clear signals of CRH1 receptor mRNA and CRH binding sites in the central amygdaloid nucleus of either group, confirming the reportedly low expression and density of CRH receptors in this brain area. The present data support the view that CRH receptors in the central nucleus of the amygdala are involved in the mediation and expression of anxiety-related behavior, but simultaneously raise questions as to the mechanisms of antisense oligodeoxynucleotide action.
我们研究了中央杏仁核促肾上腺皮质激素释放激素（CRH）受体在对致焦虑刺激的行为反应中的作用。通过渗透微型泵（0.25微克/0.5微升/小时）将与大鼠CRH1受体mRNA对应的反义寡脱氧核苷酸长期注入雄性大鼠的中央杏仁核。对照组接受乱序序列寡脱氧核苷酸或溶剂的注入。在治疗的第4天，让大鼠经历10分钟的社会挫败，随后立即在高架十字迷宫上进行测试。与接受乱序序列和溶剂处理的动物相比，接受反义寡脱氧核苷酸处理的大鼠在探索十字迷宫开放臂上花费的时间明显更多，而后两者之间没有差异。另一方面，社会辨别测试显示各治疗组之间在幼年识别能力上没有差异。通过原位杂交和受体放射自显影，我们未能在任何一组的中央杏仁核中检测到CRH1受体mRNA和CRH结合位点的清晰信号，这证实了据报道该脑区中CRH受体的低表达和低密度。目前的数据支持这样一种观点，即杏仁核中央核中的CRH受体参与焦虑相关行为的介导和表达，但同时也对反义寡脱氧核苷酸作用的机制提出了疑问。
