Published behavioral experiments document that amphetamine-induced increases in locomotor activity are preserved or enhanced in animals with major depletions of stored dopamine but intact dopamine synthesis. Conversely, amphetamine effects are substantially attenuated after inhibition of dopamine synthesis when most of the dopamine stores are preserved. Such data suggest that amphetamine mobilizes newly synthesized dopamine into extracellular signaling space. The first goal of this project is to determine kinetic parameters of dopamine secretion into and removal from extracellular space compatible with the majority of amphetamine-elicited increases in extracellular dopamine deriving from newly synthesized dopamine. The strategy uses a computational model of extracellular space surrounding a single dopamine varicosity. Model output was compared to published micro-dialysis data for effects of amphetamine on levels of extracellular dopamine. A family of solutions was found, characterized by a biphasic dose-response relationship for rate of dopamine release. Maximum rates of dopamine release occurred at doses of 0.5-1.0 mg/kg amphetamine. The second goal is to develop a hypothesis by which newly synthesized dopamine gains access to extracellular space. The model chosen involves amphetamine-induced shunting of DOPAC secretion to dopamine secretion into extracellular space. The quality of the hypothesis was evaluated by goodness of match of model output to published data for amphetamine alone and after inhibition of dopamine synthesis or storage. In summary, the results provide conditions required for and a potential mechanism for newly synthesized dopamine to be a major fraction of amphetamine-elicited increases in extracellular dopamine.

中文翻译：

---

细胞外多巴胺动力学参数与苯丙胺作用一致。

已发表的行为实验表明，苯丙胺诱导的运动能力增强在动物体内储存的多巴胺主要消耗但多巴胺合成完整的情况下得以保留或增强。相反，当大多数多巴胺储存被保留时，在抑制多巴胺合成后，苯丙胺的作用显着减弱。这些数据表明苯丙胺将新合成的多巴胺动员到细胞外信号空间。该项目的第一个目标是确定与大多数苯丙胺引起的新合成多巴胺引起的细胞外多巴胺增加的相容性有关的多巴胺分泌进入细胞外空间和从细胞外空间中去除的动力学参数。该策略使用围绕单个多巴胺静脉曲张的细胞外空间的计算模型。将模型输出与已发布的微透析数据进行比较，以了解苯丙胺对细胞外多巴胺水平的影响。发现了一系列溶液，其特征在于多巴胺释放速率的双相剂量-反应关系。多巴胺的最大释放速率发生在0.5-1.0 mg / kg苯丙胺的剂量下。第二个目标是建立一个假设，新合成的多巴胺可以进入细胞外空间。选择的模型涉及苯丙胺诱导的DOPAC分泌分流至多巴胺分泌进入细胞外空间。通过将模型输出与单独的苯丙胺以及抑制多巴胺合成或储存后的已公布数据相匹配的良好性，来评估假设的质量。综上所述，