High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat.
High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat.
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DOI：
10.1111/j.1471-4159.2011.07407.x
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发表时间：
2011-12
影响因子：
4.7
通讯作者：
Garris PA
中科院分区：
文献类型：
--
作者：
Ramsson ES;Howard CD;Covey DP;Garris PA
高剂量的安非他明（AMPH）被认为是破坏动作电位依赖性多巴胺能神经传递的正常模式，通过耗尽多巴胺（DA）的囊泡储存和诱导强大的非胞吐DA释放或通过多巴胺转运蛋白（DAT）逆转流出。然而，这些基本的AMPH行动一直难以确定在体内。在这里，我们使用快速扫描循环伏安法（FSCV）在麻醉大鼠评估的影响，10和20毫克/公斤AMPH囊泡DA释放和DAT功能的背侧和腹侧纹状体。同样高剂量的可卡因（40 mg/kg）也进行了检查，以与优先通过DAT抑制作用的精神兴奋剂进行比较。描述胞吐DA释放和神经元DA摄取的参数确定由轻度电刺激诱发的动态DA信号先前建立的是加强。使用具有纳摩尔检测的高灵敏度FSCV来监测作为DA流出指数的背景伏安信号的变化。两种剂量的AMPH和可卡因显着升高诱发DA水平在整个2小时的时间过程中，在背侧和腹侧纹状体。这些增加介导的增强囊泡DA释放和减少DA摄取通常同时起作用。AMPH，而不是可卡因，在一些基线记录中诱导了缓慢的DA样升高。然而，这种影响在幅度和持续时间上变化很大，适度，并且通常根本不存在。因此，这些数据描述了一个机械相似的激活动作电位依赖多巴胺能神经传递的AMPH和可卡因在体内。此外，DA外排似乎是一个独特的，但次要的，AMPH行动。
High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action.
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影响因子：
2.9
作者：
CHEN, GY;EWING, AG
通讯作者：
EWING, AG
影响因子：
3
作者：
Borland, LM;Shi, GY;Michael, AC
通讯作者：
Michael, AC
影响因子：
56.9
作者：
EWING, AG;BIGELOW, JC;WIGHTMAN, RM
通讯作者：
WIGHTMAN, RM
影响因子：
3.3
作者：
CARBONI, E;IMPERATO, A;DICHIARA, G
通讯作者：
DICHIARA, G
影响因子：
2.9
作者：
Anderson, BB;Chen, GY;Ewing, AG
通讯作者：
Ewing, AG