The attenuation of learning impairments induced after exposure to CO or trimethyltin in mice by sigma (σ) receptor ligands involves both σ1 and σ2 sites
The attenuation of learning impairments induced after exposure to CO or trimethyltin in mice by sigma (σ) receptor ligands involves both σ1 and σ2 sites
复制标题
DOI：
10.1038/sj.bjp.0702553
复制
发表时间：
1999-05-01
影响因子：
7.3
通讯作者：
Nabeshima, T
中科院分区：
文献类型：
--
作者：
Maurice, T;Phan, VL;Nabeshima, T
1 σ（σ）受体配体先前被报道在几种药理学和病理学的遗忘症啮齿动物模型上减轻学习和记忆障碍。这种作用被证明涉及sigma受体的sigma（1）亚型。2在这项研究中，我们表征了sigma配体介导的对小鼠两种健忘症病变模型的药理作用：（1）缺氧相关的学习和记忆障碍模型重复暴露于一氧化碳（CO）气体;三甲基锡中毒（1 mg kg（-1））。3选择性ol配体PRE-084（1 mg kg（-1））或非选择性σ（1）/σ（2）化合物DTG（0.1 mg kg（-1）），BD 1008（3毫克/千克（-1）），和氟哌啶醇（0.1毫克/千克（-1））显著逆转了暴露于CO后7天或三甲基锡中毒后14天观察到的自发交替缺陷。选择性σ 1受体拮抗剂NE-100（1 mg kg（-1））本身无效，但完全阻断PRE-084的作用，部分阻断DTG的作用，并且不影响BD 1008或氟哌啶醇诱导的作用。5在暴露于CO后8天进行的降压型被动回避试验中观察到类似的药理学特征。6这些结果表明，与先前报道的遗忘模型相反，暴露于CO或三甲基锡中毒后诱导的损伤不仅可以被σ（1）受体激动剂减轻，而且可以被σ（2）受体激动剂减轻。在这些损伤模型中观察到的神经变性的特定模式可以解释这些差异。
1 Sigma (sigma) receptor ligands were previously reported to alleviate learning and memory impairments on several pharmacological and pathological rodent models of amnesia. Such effect was demonstrated as involving the sigma(1) subtype of sigma receptor.2 In this study, we characterized the pharmacological effect mediated by sigma ligands on two lesional models of amnesia in mice: (1) the hypoxia-related learning and memory impairment model induced by repeated exposure to carbon monoxide (CO) gas; and (2) the intoxication with trimethyltin (1 mg kg(-1)).3 The selective ol ligand PRE-084 (1 mg kg(-1)) or the non-selective sigma(1)/sigma(2) compounds DTG (0.1 mg kg(-1)), BD1008 (3 mg kg(-1)), and haloperidol (0.1 mg kg(-1)) reversed significantly the spontaneous alternation deficits observed 7 days after exposure to CO or 14 days after intoxication with trimethyltin.4 The selective sigma(1) receptor antagonist NE-100 (1 mg kg(-1)) was ineffective by itself, but blocked completely the PRE-084 effects, partially the DTG effects, and did not affect the effects induced by BD1008 or haloperidol.5 A similar pharmacological profile was observed in the step-down type passive avoidance test performed 8 days after exposure to CO.6 These results show that, in contrast to the previously reported amnesia models, the impairments induced after exposure to CO or intoxication with trimethyltin could be alleviated not only by sigma(1) receptor agonists but also by sigma(2) agonists. The particular pattern of neurodegeneration observed in these lesional models may explain these differences.