Drug dependence, synaptic plasticity, and tissue plasminogen activator.
Drug dependence, synaptic plasticity, and tissue plasminogen activator.
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药物依赖性、突触可塑性和组织纤溶酶原激活剂。
DOI：
10.1254/jphs.cp0040014
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发表时间：
2005
影响因子：
3.5
通讯作者：
T. Nabeshima
中科院分区：
文献类型：
--
作者：
Kiyofumi Yamada;T. Nagai;T. Nabeshima
中皮质边缘多巴胺能系统在药物滥用的强化效应中起重要作用，该系统的活性依赖性突触可塑性参与药物依赖。DNA芯片检测显示，与对照组相比，吗啡或甲基苯丙胺依赖大鼠伏隔核组织纤溶酶原激活物(TPA)mRNA的表达水平显著升高。由于tPA在突触可塑性中起作用，我们推测tPA可能与药物依赖的发展有关。单次和重复吗啡处理以及重复甲基苯丙胺处理可诱导伏隔核内tPA基因的表达，并与酶活性增加有关。在tPA基因定向缺失的小鼠(tPA-/-小鼠)中，吗啡诱导的条件性位置偏爱显著降低，并伴随着吗啡诱导的多巴胺释放的丧失。同样，甲基苯丙胺诱导的条件性位置偏爱和运动敏感化在tPA-/-小鼠中也减少。向伏核内微量注射外源性tPA或纤溶酶可逆转吗啡诱导的多动和甲基苯丙胺诱导的tPA-/-小鼠运动敏化的缺陷。这些结果支持了我们的假设，即tPA在与药物依赖相关的长期神经元变化中发挥作用。
The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the system is involved in drug dependence. A DNA microarray screening revealed that the expression levels of tissue plasminogen activator (tPA) mRNA in the nucleus accumbens of morphine- or methamphetamine-dependent rats were significantly increased compared with those in control animals. Since tPA plays a role in synaptic plasticity, we hypothesized that tPA may contribute to the development of drug dependence. Single and repeated morphine treatment as well as repeated methamphetamine treatment induced tPA mRNA expression in the nucleus accumbens, which was associated with an increase in the enzyme activity. Conditioned place preference induced by morphine was markedly reduced in mice with a targeted deletion of the tPA gene (tPA-/- mice), being accompanied by a loss of morphine-induced dopamine release. Similarly, methamphetamine-induced conditioned place preference and locomotor sensitization were reduced in tPA-/- mice. The defects of morphine-induced hyperlocomotion as well as methamphetamine-induced locomotor sensitization in tPA-/- mice were reversed by microinjection of exogenous tPA or plasmin into the nucleus accumbens. These results support our hypothesis that tPA plays a role in long-lasting neuronal changes related to drug dependence.
影响因子：
4.6
作者：
Pamela M. Carroll;Stella E. Tsirka;William G. Richards;M. A. Frohman;Sidney Strickland
通讯作者：
Pamela M. Carroll;Stella E. Tsirka;William G. Richards;M. A. Frohman;Sidney Strickland
药物的辨别刺激特性与主观效果之间的关系。
DOI：
10.1007/978-3-642-73223-2_13
发表时间：
1988
期刊：
Psychopharmacology series
影响因子：
--
作者：
Schuster,CR;Johanson,CE
通讯作者：
Johanson,CE