INTRACELLULAR STUDIES ON THE DOPAMINE-INDUCED FIRING INHIBITION OF NEOSTRIATAL NEURONS INVITRO - EVIDENCE FOR D1-RECEPTOR INVOLVEMENT
INTRACELLULAR STUDIES ON THE DOPAMINE-INDUCED FIRING INHIBITION OF NEOSTRIATAL NEURONS INVITRO - EVIDENCE FOR D1-RECEPTOR INVOLVEMENT
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DOI：
10.1016/0306-4522(87)90239-9
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发表时间：
1987-03-01
期刊：
影响因子：
3.3
通讯作者：
BERNARDI, G
中科院分区：
文献类型：
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作者：
CALABRESI, P;MERCURI, N;BERNARDI, G
从大鼠新纹状体切片获得细胞内记录。施加的多巴胺（1-10 μ M）产生对由直接刺激诱发的动作电位的可逆抑制和纹状体内诱发的去极化突触后电位的幅度的降低。在施加1-10 μ M多巴胺的过程中没有检测到膜电位的变化。多巴胺的应用也产生了减少异常整流的去极化方向。这种阈下内向整流作用可被河豚毒素所抑制，但不被无钙和含镉（0.1-1 mM）溶液所抑制。多巴胺诱导的兴奋性突触后电位振幅的减少在静息膜电位或更积极的水平是明显的，但不存在在超极化值的膜电位。向培养基中加入荷包牡丹碱（50-500 μ M）不影响多巴胺的抑制作用。多巴胺的抑制作用也坚持在无钙和含镉的解决方案。腺苷3“，5”-环一磷酸类似物，8-溴-腺苷3“，5”-环一磷酸（0.1 mM），模拟D1受体激活产生的作用。浴涂2，3，5，5-四氢-7，8-二羟基-1-苯基-1H-3-苯并氮杂（SKF 38393）（1-10 μ M），一种选择性D1多巴胺能激动剂，模拟微摩尔浓度的多阿明的作用。D2多巴胺能激动剂4，4 α，5，6，7，8，8 α，9-八氢-5-正丙基-2-H-吡唑并-3，4-g-喹啉（LY 171555）和溴隐亭（均为10 nM-10 μ M）对新生层细胞没有作用。微摩尔剂量的多巴胺或SKF 38393诱导的抑制作用被R-（+）-8-氯-2，3，4，5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂庚因-7-醇（SCH 23390; 0.1-10 μ M）（一种D1-选择性拮抗剂）的浴用所拮抗，但不被舒必利（10 nM-10 μ M）（一种D2拮抗剂）所拮抗。我们的结论是，多巴胺对大鼠纹状体神经元的抑制作用是突触后介导的D1多巴胺能受体的激活，通过减少电压依赖性河豚毒素敏感的内向电导。
Intracellular recordings were obtained from rat neostriatal slices. Bath-applied dopamine (1-10 .mu.M) produced a reversible inhibition of the action potentials evoked by direct stimulation and a decrease in the amplitude of the intrastriatally evoked depolarizing postsynaptic potentials. No change in membrane potential was detected during the applciation of 1-10 .mu.M dopamine. Dopamine application also produced a decrease in anomalous rectification in the depolarizing direction. This subthreshold inward rectification was abolsihed by tetrodotoxin, but not by calcium-free and cadmium (0.1-1 mM)-containing solutions. The dopamine-induced decrease in excitatory postsynaptic potential amplitude was evident at resting membrane potential or at more positive levels, but was absent at hyperpolarized values of the membrane potential. Addition of bicuculline (50-500 .mu.M) to the medium did not affect the inhibitory action of dopamine. The inhibitory action of dopamine also persisted in calcium-free and cadmium-containing solutions. The adenosine 3'',5''-cyclic monophosphate analogue, 8-bromo-adenosine 3'',5''-cyclic monophosphate (0.1- mM), mimicked the effects produced by D1 receptor activation. Bath application of 2,3,5,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393) (1-10 .mu.M), a selective D1 dopaminergic agonist, mimicked the effects of micromolar concentrations of doapmine. The D2 doapminergic agonists, 4,4a,5,6,7,8,8a,9-octahydro-5-n-propyl-2-H-pyrazolo-3,4-g-quinoline (LY 171555) and bromocriptine (both at 10 nM-10 .mu.M), had no effects on neostratal cells. The inhibition induced by micromolar doses of dopamine or SKF 38393 was antagonized by bath applications of R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390; 0.1-10 .mu.M), a D1-selective antagonist, but not by sulpiride (10 nM-10 .mu.M), a D2 antagonist. We conclude that the inhibitory effect of dopamine on rat striatal neurons is postsynaptically mediated by the activation of D1 dopaminergic receptors via the reduction of a voltage-dependent tetrodotoxin-sensitive inward conductance.