Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.
Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.
复制标题
安非他明增强体内纹状体中动作电位依赖性多巴胺能信号传导。
DOI：
10.1111/j.1471-4159.2011.07258.x
复制
发表时间：
2011
影响因子：
4.7
通讯作者：
Garris,PaulA
中科院分区：
文献类型：
--
作者：
Ramsson,EricS;Covey,DanielP;Daberkow,DavidP;Litherland,MelissaT;Juliano,StevenA;Garris,PaulA
J. Neurochem.(2011)117, 937–948. 摘要安非他明 (AMPH) 被认为通过消耗多巴胺 (DA) 囊泡储存和促进非胞吐 DA 外流来破坏动作电位依赖性多巴胺能信号传导的正常模式。脑切片伏安法同时证明了这些关键的药物作用，以及神经元 DA 摄取的竞争性抑制。在这里，我们在体内进行了类似的动力学和伏安分析，以确定 AMPH 在完整大脑中的作用在质量和数量上是否相似。快速扫描循环伏安法测量了聚氨酯麻醉大鼠背侧和腹侧纹状体的细胞外 DA。分析电诱发记录以确定 DA 摄取和囊泡 DA 释放的 Kman 和 Vmax，同时背景伏安电流指示基础 DA 浓度。 AMPH（腹腔注射 0.5、3 和 10mg/kg）可显着增加两个纹状体亚区域的诱发 DA 反应。导致这些水平升高的主要因素是竞争性摄取抑制，因为腹侧纹状体的胞吐释放没有变化，而背侧纹状体的胞吐释放仅略有减少。未检测到基础 DA 水平的增加。这些结果与 AMPH 在广泛的行为相关剂量范围内增强体内动作电位依赖性多巴胺能信号传导一致。未来的工作应针对 AMPH 独特的体外和体内药理学的可能原因。
J. Neurochem.(2011)117, 937–948.AbstractAmphetamine (AMPH) is thought to disrupt normal patterns of action potential‐dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non‐exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here, we perform comparable kinetic and voltammetric analysesin vivoto determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast‐scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane‐anesthetized rats. Electrically evoked recordings were analyzed to determineKmandVmaxfor DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential‐dependent dopaminergic signalingin vivoacross a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinctin vitroandin vivopharmacology of AMPH.