Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones
Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones
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DOI：
10.1111/j.1469-7793.2000.t01-2-00163.x
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发表时间：
2000-02-15
影响因子：
5.5
通讯作者：
Momiyama, T
中科院分区：
文献类型：
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作者：
Koga, E;Momiyama, T
1. 使用全细胞膜片钳技术在大鼠中脑切片中检查多巴胺 (DA) 对腹侧被盖区 (VTA) 多巴胺能神经元的非 NMDA 谷氨酸能传递的影响。在荷包牡丹碱 (20 μM)、士的宁 (0.5 μM) 和 D-氨基-5-膦基戊酸 (D-AP5，25 μM) 存在下，5 μM CNQX 可逆地阻断 VTA 内局灶性刺激诱发的多巴胺能神经元中的 EPSC。2． DA 浴的应用以浓度依赖性方式在 0.3-1000 μM（IC50，16.0 μM）之间将 EPSC 的振幅降低了 65.1 +/- 9.52%，而不影响使用 Cs+ 填充电极测量的 -60 mV 的保持电流。 3． DA 对诱发 EPSC 的作用可被 D-2 样受体激动剂喹吡罗模拟，但不能被 D-1 样受体激动剂 SKF 81297 模拟，并且被 D-2 样受体拮抗剂舒必利 (K-B，0.96 μM) 拮抗，但不能被 D-1 样受体拮抗剂 SCH 23390 (K-B， 228.6亩).4．多巴胺(30μM)降低了自发微型EPSCs(mEPSCs)的平均频率，但不影响其平均振幅，并且DB对mEPSCs的诱导作用取决于外部Ca2+浓度。5．这些结果表明，终止于 VTA 多巴胺能神经元的传入谷氨酸纤维具有突触前 D-2 样受体，其激活通过减少 Ca2+ 流入来抑制谷氨酸释放。
1. The effects of dopamine (DA) on non-NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole-cell patch-clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 mu M CNQX in the presence of bicuculline (20 mu M), strychnine (0.5 mu M) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 mu M).2. Bath application of DA reduced the amplitude of EPSCs up to 65.1 +/- 9.52% in a concentration-dependent manner between 0.3-1000 mu M (IC50, 16.0 mu M) without affecting the holding current at -60 mV measured using a Cs+-filled electrode.3. The effect of DA on evoked EPSCs was mimicked by the D-2-like receptor agonist quinpirole but not by the D-1-like receptor agonist SKF 81297, and was antagonized by the D-2-like receptor antagonist sulpiride (K-B, 0.96 mu M), but not by the D-1-like receptor antagonist SCH 23390 (K-B, 228.6 mu M).4. Dopamine (30 mu M) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DB-induced effect on the mEPSCs was dependent on the external Ca2+ concentration.5. These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D-2-like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.