Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies
Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies
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DOI：
10.1016/s0006-8993(98)01040-3
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发表时间：
1998-12-14
期刊：
影响因子：
2.9
通讯作者：
Gnegy, ME
中科院分区：
文献类型：
--
作者：
Browman, KE;Kantor, L;Gnegy, ME
安非他明产生增强的运动活性的能力被认为是由于它能够增强中脑边缘多巴胺神经元的多巴胺释放。安非他明增加多巴胺释放的机制尚不清楚，但被认为涉及通过多巴胺转运蛋白与突触体多巴胺的交换扩散。我们最近报道，安非他明介导的多巴胺释放在纹状体也依赖于蛋白激酶C的活性。在目前的研究中，我们研究了蛋白激酶C活性的作用，在急性神经化学和行为反应安非他明在延髓核。与先前在纹状体中的结果一致，安非他明刺激的多巴胺从丘脑核组织的释放被特异性蛋白激酶C抑制剂Ro 31 -8220抑制，但不被相对无活性的类似物双吲哚酰马来酰亚胺V抑制。用Ro 31 - 2注射法检测蛋白激酶C活性对苯丙胺急性行为反应的影响。8220注入丘脑核15 min后再注入苯丙胺。相对于用溶剂预处理的对照受试者，用Ro 31 -8220预处理减弱了内给药苯丙胺的运动刺激作用。双吲哚酰马来酰亚胺V没有显着抑制运动兴奋作用的内苯异丙胺。这些结果表明，安非他明的行动，在增加多巴胺的释放和自发活动的延髓核是依赖于蛋白激酶C的活性。(C)1998 Elsevier Science B. V.保留所有权利。
The ability of amphetamine to produce heightened locomotor activity is thought to be due to its ability to enhance dopamine release from mesolimbic dopamine neurons. The mechanism by which amphetamine increases dopamine release is not well understood, but is thought to involve exchange diffusion with synaptosomal dopamine through the dopamine transporter. We recently reported that amphetamine-mediated dopamine release in the striatum is also dependent on protein kinase C activity. In the current study, we investigated the role of protein kinase C activity in the acute neurochemical and behavioral response to amphetamine in the nucleus accumbens. Consistent with previous results in the striatum, amphetamine-stimulated dopamine release from nucleus accumbens tissue was inhibited by the specific protein kinase C inhibitor Ro31-8220, but not by the relatively inactive analog bisindoylmaleimide V. Ln addition, the effects of protein kinase C activity on the acute behavioral response to amphetamine was examined by injecting Ro31-8220 into the nucleus accumbens 15 min prior to intra-accumbens amphetamine. Pretreatment with Ro31-8220 attenuated the motor-stimulant effects of intra-accumbens amphetamine relative to control subjects pretreated with vehicle. Bisindoylmaleimide V did not significantly inhibit the motor-stimulant effects of intra-accumbens amphetamine. These results suggest that the action of amphetamine in the nucleus accumbens in increasing dopamine release and locomotor activity is dependent on protein kinase C activity. (C) 1998 Elsevier Science B.V. All rights reserved.