Björklund M, Sirviö J, Riekkinen M, Sallinen J, Scheinin M, Riekkinen P
Department of Neurology and Neuroscience, University of Kuopio, Finland.
Neuroscience. 2000;95(2):481-7. doi: 10.1016/s0306-4522(99)00428-5.
We investigated the role of overexpression of alpha2C-adrenoceptors in water maze navigation in mice transgenically manipulated to have a threefold overexpression of the alpha2C-adrenoreceptors. Alpha2C-adrenoreceptors overexpressing mice swam more in the peripheral annulus of the pool and did not find the hidden escape platform as well as the wild type control mice. A subtype-nonselective alpha2-adrenoreceptor antagonist, atipamezole (ATI, 1000 microg/kg, s.c.), fully reversed the deficit in platform finding and search strategy in overexpressing mice. Noradrenaline depletion (-95%) induced by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) did not impair platform finding of wild type or overexpressing mice. The DSP-4 lesion slightly increased swimming in the peripheral annulus in wild type mice, but not in overexpressing mice. The DSP-4 lesion produced a dissociable effect on the action of atipamezole to improve platform finding and search strategy in overexpressing mice: atipamezole did not alleviate the platform finding deficit in DSP-4 lesioned overexpressing mice, but normalized their abnormal search strategy. These results suggest that the abnormal search pattern and deficit in the accuracy of platform finding are mediated by constitutive activity of overexpressed alpha2C-adrenoreceptors.
我们研究了α2C-肾上腺素能受体过表达在经转基因操作使α2C-肾上腺素能受体过表达三倍的小鼠水迷宫导航中的作用。过表达α2C-肾上腺素能受体的小鼠在水池外周环中游泳的时间更长，并且与野生型对照小鼠相比，未能找到隐藏的逃生平台。一种亚型非选择性α2-肾上腺素能受体拮抗剂阿替美唑（ATI，1000μg/kg，皮下注射）完全逆转了过表达小鼠在寻找平台和搜索策略方面的缺陷。由N-（2-氯乙基）-N-乙基-2-溴苄胺（DSP-4）诱导的去甲肾上腺素耗竭（-95%）并未损害野生型或过表达小鼠寻找平台的能力。DSP-4损伤使野生型小鼠在外周环中的游泳略有增加，但对过表达小鼠没有影响。DSP-4损伤对阿替美唑改善过表达小鼠寻找平台和搜索策略的作用产生了可分离的影响：阿替美唑并未减轻DSP-4损伤的过表达小鼠在寻找平台方面的缺陷，但使其异常搜索策略正常化。这些结果表明，异常搜索模式和寻找平台准确性的缺陷是由过表达的α2C-肾上腺素能受体的组成性活性介导的。
