Analysis of function of dopamine as a retrograde messenger in the basal ganglia

利用小鼠中脑切片进行全细胞膜片钳研究，阐明多巴胺（DA）的生理作用（P13-21）。非nmda谷氨酸受体介导的EPSCs在-60 mV保持电位的局灶刺激下在腹侧被盖多巴胺能神经元中被激活。0 mV去极化脉冲5 s对野生型小鼠EPSCs的抑制作用为42.8±3.1% （n=16）。在沐浴液中加入d2样受体拮抗剂舒匹利（5 μM）后，去极化诱导的EPSCs （DSE）抑制幅度显著（P<0.05）降低至7.3±9.9% （n=5）。D2受体缺陷小鼠的DSE波幅也明显（P<0.05）小（7.3±2.0%,n=17）。去极化脉冲在电流箝位模式下产生动作电位（36.5±5.9%,n=5）观察到DSE。这些结果表明，多巴胺能神经元释放的DA作用于突触前D2受体抑制谷氨酸释放，暗示DA在中枢神经系统中作为逆行信使的作用。

Whole-cell patch-clamp study was carried out to elucidate physiological roles of dopamine (DA) using midbrain slices of the mice (P13-21). EPSCs mediated by non-NMDA glutamate receptors were evoked in the ventral tegmental dopaminergic neurons by focal stimulation at the holding potential of -60 mV. Application of a depolarizing pulse to 0 mV for 5 s inhibited the EPSCs by 42.8 ± 3.1% (n=16) in wild type mice. The magnitude of depolarization-induced inhibition of EPSCs (DSE) was significantly (P<0.05) reduced to 7.3 ± 9.9% (n=5) in the presence of a D2-like receptor antagonist, sulpiride (5 μM), in the bathing solution. DSE amplitude was also significantly (P<0.05) small in slices obtained from D2 receptor deficient mice (7.3 ± 2.0%, n=17). DSE was also observed by action potential generation induced by depolarizing pulses in the current-clamp mode (36.5 ± 5.9%, n=5). These results suggest that DA released from dopaminergic neurons acts on presynaptic D2 receptors to inhibit glutamate release, implying a role of DA as a retrograde messenger in the central nervous system.