Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype
Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype
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DOI：
10.1016/j.bbr.2003.12.016
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发表时间：
2004-08-31
影响因子：
2.7
通讯作者：
Ghelardini, C
中科院分区：
文献类型：
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作者：
Galeotti, N;Bartolini, A;Ghelardini, C
据报道，α 2肾上腺素受体的激活会损害大鼠和人类的记忆功能。负责这种有害作用的α（2）-肾上腺素受体亚型仍然未知。在小鼠被动回避试验中评价了α（2）-激动剂可乐定和胍那苄对记忆过程的影响，其与给药时间的依赖性。可乐定（0.02 - 0.2 mg kg（-1）i.p.）和胍那苄（0.1 - 0.3mg kg（-1）i.p.）以剂量依赖性方式诱发失忆症。从时间过程的实验中发现，只有可乐定和胍那苄在训练测试前60分钟或训练测试后立即给药时，才能检测到记忆功能的损害。这种有害作用可通过预先给予α 2受体拮抗剂育亨宾（1 - 3 mg kg（-1）i.p.）和α（2A）-拮抗剂BRL-44408（0.3 - 1 mg kg（-1）i.p.）。相比之下，α（2B），（C）拮抗剂ARC-239（10 mg kg（-1）i.p.）和哌唑嗪（1 mg kg（-1）i.p.）并不能逆转可乐定和胍那苄引起的失忆。在最高有效剂量，可乐定和胍那苄没有行为副作用，以及保持不变的运动协调，所揭示的旋转杆测试。此外，如Animex装置所示，所用化合物均未改变自发运动性。这些结果表明，可乐定和胍那苄通过选择性激活α（2A）-肾上腺素受体亚型在小鼠被动回避范例中损害记忆过程。(C)2004 Elsevier B.V.保留所有权利。
The activation of alpha(2)-adrenoceptors has been reported to impair memory functions in both rats and humans. The alpha(2)-adrenoceptor subtype responsible for this detrimental effect is still unknown. The effect of the alpha(2)-agonists clonidine and guanabenz on memory processes, in dependence to the time of administration, was evaluated in the mouse passive avoidance test. Clonidine (0.02-0.2 mg kg(-1) i.p.) and guanabenz (0.1-0.3 mg kg(-1) i.p.) induced amnesia in a dose-dependent manner. From time-course experiments emerged that the impairment of memory function was detectable only when clonidine and guanabenz were administered 60 min before or immediately after the training test, respectively. This detrimental effect was prevented by pretreatment with the alpha(2)-antagonist yohimbine (1-3 mg kg(-1) i.p.) and by the alpha(2A)-antagonist BRL-44408 (0.3-1 mg kg(-1) i.p.). By contrast, the alpha(2B),(C) antagonists ARC-239 (10 mg kg(-1) i.p.) and prazosin (1 mg kg(-1) i.p.) did not revert the amnesia induced by both clonidine and guanabenz. At the highest effective doses, clonidine and guanabenz were devoid of behavioral side-effects as well as maintained unaltered the motor coordination, as revealed by the rota-rod test. Furthermore, none of the compounds used modified the spontaneous motility as indicated by the Animex apparatus. These results indicate that clonidine and guanabenz impaired memory processes in a mouse passive avoidance paradigm through the selective activation of the alpha(2A) -adrenoceptor subtype. (C) 2004 Elsevier B.V. All rights reserved.