Tanila H, Mustonen K, Sallinen J, Scheinin M, Riekkinen P
Department of Neuroscience and Neurology, University and University Hospital of Kuopio, Finland.
Eur J Neurosci. 1999 Feb;11(2):599-603. doi: 10.1046/j.1460-9568.1999.00464.x.
The role of the alpha2C-adrenoceptor subtype in mediating the beneficial effect of alpha2-adrenoceptor agonists on spatial working memory was studied in adult mice with targeted inactivation of the alpha2C-receptor gene (KO) and their wild-type controls (WT). A delayed alternation task was run in a T-maze with mixed delays varying from 20 s to 120 s. Dexmedetomidine, a specific but subtype nonselective alpha2-adrenoceptor agonist, dose-dependently decreased the total number of errors. The effect was strongest at the dose of 5 microg/kg (s.c.), and was observed similarly in KO and WT mice. KO mice performed inferior to WT mice due to a higher number of perseverative errors. Dexmedetomidine slowed initiation of the motor response in the start phase at lower doses in WT mice than in KO mice but no such difference was observed in the return phase of the task, suggesting involvement of alpha2C-adrenoceptors in the cognitive aspect of response preparation or in response sequence initiation. According to these findings, enhancement of spatial working memory is best achieved with alpha2-adrenoceptor agonists which have neither agonistic nor antagonistic effects at the alpha2C-adrenoceptor subtype.
在α2C -肾上腺素能受体基因靶向失活的成年小鼠（KO）及其野生型对照（WT）中，研究了α2C -肾上腺素能受体亚型在介导α2 -肾上腺素能受体激动剂对空间工作记忆的有益作用中的作用。在T型迷宫中进行延迟交替任务，混合延迟时间从20秒到120秒不等。右美托咪定是一种特异性但非亚型选择性的α2 -肾上腺素能受体激动剂，剂量依赖性地减少了总错误数。在5微克/千克（皮下注射）剂量时效果最强，在KO小鼠和WT小鼠中观察到的效果相似。由于持续性错误数量较多，KO小鼠的表现不如WT小鼠。在较低剂量时，右美托咪定使WT小鼠起始阶段的运动反应启动比KO小鼠更慢，但在任务的返回阶段未观察到这种差异，这表明α2C -肾上腺素能受体参与了反应准备的认知方面或反应序列的启动。根据这些发现，对于α2C -肾上腺素能受体亚型既无激动作用也无拮抗作用的α2 -肾上腺素能受体激动剂，能最好地增强空间工作记忆。
