Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro
Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro
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DOI：
10.1159/000111247
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发表时间：
1997-11-01
影响因子：
2.9
通讯作者：
Levine, MS
中科院分区：
文献类型：
--
作者：
Cromwell, HC;King, BH;Levine, MS
佩莫林是一种中枢兴奋剂，全身高剂量(300毫克/公斤)可可靠地在大鼠身上产生自咬行为。佩莫林引起的自咬症与某些人类疾病中的自伤有许多相似之处。最近的证据表明，新纹状体神经化学的变化伴随着大鼠的自咬行为。本研究利用细胞内电生理技术，揭示了自伤大鼠脑片中新纹状体细胞生理学的变化。对接受匹莫林并一直有自残行为的大鼠和来自两个对照组的新纹状体切片中的去极化突触后电位(DPSPs)进行了检测：接受相同浓度的佩莫林但不进行自咬的大鼠，以及只接受赋形剂(花生油)的大鼠。数据采集在标准人工脑脊液中。皮层电刺激脑片诱发DPSP。在接受载体或接受匹莫林但没有自我损伤的大鼠的神经元中，应用多巴胺(DA，20muM)可显著缩小皮质诱发的新纹状体DPSP的大小。相比之下，多巴胺的应用增加了服用匹莫林并进行自我损伤的大鼠神经元中DPSP的大小。联合应用D-1和D-2受体激动剂最佳地复制了DA的增强效应。此外，竞争性N-甲基-D-天冬氨酸受体拮抗剂2-氨基-5-膦戊酸可阻断这种增强作用。结果表明，新纹状体DA-谷氨酸相互作用的改变伴随着佩莫林注射而产生的自我伤害行为。
Pemoline, a central stimulant, administered systemically at high doses (300 mg/kg) reliably produces self-biting behavior in rats. Pemoline-induced self-biting shares many similarities with self-injury seen in certain human disorders. Recent evidence has shown that alterations in neostriatal neurochemistry accompany the self-biting behavior seen in the rat. The present study used intracellular electrophysiological techniques to reveal changes in neostriatal cellular physiology in slices from rats which had displayed self-injury. Depolarizing postsynaptic potentials (DPSPs) were examined in neostriatal slices from rats that received pemoline and had been engaging in self-injurious behavior and from two control populations: rats that received the same concentration of pemoline and did not engage in self-biting, and rats that received vehicle alone (peanut oil). Data were acquired in standard artificial cerebral spinal fluid. DPSPs were evoked by cortical electrical stimulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dopamine (DA, 20 mu M) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA application produced an increase in DPSP size in neurons from rats which had received pemoline and had engaged in self-injury. Bath application of a combination of D-1 and D-2 receptor agonists best replicated the enhancing effect of DA. Furthermore, the enhancement could be blocked by pretreatment with the competitive N-methyl-d-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid. The results indicate that alterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.