State Key Laboratory of Biomembrane and Membrane Biotechnology and the Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
Neurochem Int. 2013 Jan;62(1):50-7. doi: 10.1016/j.neuint.2012.11.006. Epub 2012 Nov 16.
The ambient resting dopamine (DA) concentration in brain regulates cognition and motivation. Despite its importance, resting DA level in vivo remains elusive. Here, by high-frequency stimulation of the medial forebrain bundle and immediately following the stimulus-induced DA overflow, we recorded a DA "undershoot" which is a temporal reduction of DA concentration to a level below the baseline. Based on the DA undershoot, we predicted a resting DA concentration of ∼73nM in rat striatum in vivo. Simulation studies suggested that removing basal DA by DAT during the post-stimulation inhibition of tonic DA release caused the DA undershoot, and the resting concentration of DA modulated the kinetics of the evoked DA transient. The DA undershoot was eliminated by either blocking D2 receptors with haloperidol or blocking the DA transporter (DAT) with cocaine. Therefore, the impulse-dependent resting DA concentration is in the tens of nanomolar range and is modulated by the presynaptic D2 receptors and the DAT in vivo.
大脑环境静息多巴胺 (DA) 浓度调节认知和动机。尽管其重要性不言而喻,但体内静息 DA 水平仍然难以捉摸。在这里,通过对中脑束的高频刺激,并在刺激诱导的 DA 溢出后立即进行,我们记录到了 DA“下冲”,这是 DA 浓度暂时降低到低于基线的水平。基于 DA 下冲,我们预测大鼠纹状体体内静息 DA 浓度约为 73nM。模拟研究表明,在刺激诱导的 tonic DA 释放的抑制期间,通过 DAT 去除基础 DA 导致了 DA 下冲,并且 DA 的静息浓度调节了诱发的 DA 瞬变的动力学。用氟哌啶醇阻断 D2 受体或用可卡因阻断多巴胺转运体 (DAT) 均可消除 DA 下冲。因此,脉冲依赖性静息 DA 浓度在数十纳摩尔范围内,受体内突触前 D2 受体和 DAT 的调节。