The effect of acute and chronic LY 277359, a selective 5-HT3 receptor antagonist, on the number of spontaneously active midbrain dopamine neurons.
The effect of acute and chronic LY 277359, a selective 5-HT3 receptor antagonist, on the number of spontaneously active midbrain dopamine neurons.
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急性和慢性 LY 277359（一种选择性 5-HT3 受体拮抗剂）对自发活动的中脑多巴胺神经元数量的影响。
DOI：
10.1016/0014-2999(91)90163-k
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发表时间：
1991
影响因子：
5
通讯作者：
Wang,RY
中科院分区：
文献类型：
--
作者：
Minabe,Y;AshbyJr,CR;Wang,RY
在这项研究中，我们研究了急性和慢性给药LY 277359，一个假定的5-HT 3受体拮抗剂，对自发活动的多巴胺细胞的数量在黑质pars腹侧被盖区（VTA或A10）和黑质pars腹侧被盖区（SNC或A9）的影响。这是使用标准的细胞外单个单位记录技术完成的。LY 277359（0.1或1.0 mg/kg i.p.）与盐水对照相比，产生了自发活性A10多巴胺细胞数量的显著增加，但没有A9多巴胺细胞。10 mg/kg LY 277359急性给药未显著改变任一区域中自发活性多巴胺细胞的数量。与其急性效应相反，每天给予0.1 mg/kg LY 277359 21天，可减少自发活性A9和A10多巴胺细胞的数量。然而，静脉注射（±）-阿扑吗啡（50 μg/kg）并未逆转LY 277359的作用，表明LY 277359诱导的多巴胺细胞的慢性减少不是去极化阻滞的结果。为了测试长期给予高剂量LY 277359是否会诱导多巴胺细胞的去极化阻滞，用1.0或10 mg/kg LY 277359处理大鼠。有趣的是，1.0 mg/kg LY 277359的长期给药增加了A10多巴胺细胞的数量，但没有A9多巴胺细胞的数量。相比之下，10 mg/kg的长期治疗选择性地减少了自发活性A10多巴胺细胞的数量。相比之下，10 mg/kg的长期治疗选择性地减少了自发活性A10多巴胺细胞的数量。总体而言，我们的研究结果表明，慢性LY对中脑多巴胺神经元的剂量反应是双相的，LY 277359产生的自发活性多巴胺细胞数量的减少不是由于去极化失活。
In this study, we have examined the effect of acute and chronic administration of LY 277359, a putative 5-HT3receptor antagonist, on the number of spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmental area (VTA or A10). This was accomplished using the standard extracellular single unit recording techniques. The acute administration of LY 277359 (0.1 or 1.0 mg/kg i.p.) produced a significant increase in the number of spontaneously active A10, but not A9, dopamine cells compared to saline controls. The acute administration of 10 mg/kg of LY 277359 did not significantly alter the number of spontaneously active dopamine cells in either area. In contrast to its acute effects, the administration of 0.1 mg/kg per day of LY 277359 for 21 days decreased the number of spontaneously active A9 and A10 dopamine cells. However, the i.v. administration of (±)-apomorphine (50 μg/kg) did not reverse LY 277359's action, suggesting that the chronic LY 277359-induced reduction of dopamine cells was not the result of depolarization block. To test whether chronic administration of LY 277359 at a high dose would induce depolarization block of dopamine cells, rats were treated with 1.0 or 10 mg/kg LY 277359. Interestingly, the chronic administration of 1.0 mg/kg LY 277359 increased the number of A10, but not A9 dopamine cells. In contrast, chronic treatment with 10 mg/kg selectively decreased the number of spontaneously active A10 dopamine cells. In contrast, chronic treatment with 10 mg/kg selectively decreased the number of spontaneously active A10 dopamine cells. Overall, our results suggest that the dose response of chronic LY on midbrain dopamine neurons is biphasic and the reduction of the number of spontaneously active dopamine cells produced by LY 277359 is not due to depolarization inactivation.