Yamamoto B K, Novotney S
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
J Neurochem. 1998 Jul;71(1):274-80. doi: 10.1046/j.1471-4159.1998.71010274.x.
There is growing evidence of an interaction between dopamine and norepinephrine. To test the hypothesis that norepinephrine terminals are involved in the uptake and removal of dopamine from the extracellular space, the norepinephrine uptake blocker desmethylimipramine (DMI) was infused locally while the extracellular concentrations of dopamine were simultaneously monitored. DMI increased the extracellular concentrations of dopamine in the medial prefrontal cortex and nucleus accumbens shell but had no effect in the striatum. The combined systemic administration of haloperidol and the local infusion of DMI produced an augmented increase in extracellular dopamine in the cortex compared with the increase produced by either drug alone. This synergistic increase in dopamine overflow is likely due to the combination of impulse-mediated dopamine release produced by haloperidol and blockade of the norepinephrine transporter. No such synergistic effects were observed in the nucleus accumbens and striatum. Local perfusion of the alpha2-antagonist idazoxan also increased the extracellular concentrations of dopamine in the cortex. Although the stimulation of extracellular dopamine by idazoxan and DMI could be due to the increased extracellular concentrations of norepinephrine produced by these drugs, an increase in dopamine also was observed in lesioned rats that were depleted of norepinephrine and challenged with haloperidol. This contrasted with the lack of an effect of haloperidol on cortical dopamine in unlesioned controls. These results suggest that norepinephrine terminals regulate extracellular dopamine concentrations in the medial prefrontal cortex and to a lesser extent in the nucleus accumbens shell through the uptake of dopamine by the norepinephrine transporter.
越来越多的证据表明多巴胺与去甲肾上腺素之间存在相互作用。为了验证去甲肾上腺素终末参与从细胞外空间摄取和清除多巴胺这一假说，在局部注入去甲肾上腺素摄取阻滞剂去甲丙咪嗪（DMI）的同时，同步监测多巴胺的细胞外浓度。DMI增加了内侧前额叶皮质和伏隔核壳部的多巴胺细胞外浓度，但对纹状体没有影响。与单独使用任何一种药物相比，联合全身给予氟哌啶醇和局部注入DMI使皮质中的细胞外多巴胺增加幅度更大。多巴胺溢出的这种协同增加可能是由于氟哌啶醇产生的冲动介导的多巴胺释放与去甲肾上腺素转运体的阻断相结合所致。在伏隔核和纹状体中未观察到这种协同效应。α2拮抗剂咪唑克生的局部灌注也增加了皮质中的多巴胺细胞外浓度。虽然咪唑克生和DMI对细胞外多巴胺的刺激可能是由于这些药物使去甲肾上腺素细胞外浓度增加所致，但在去甲肾上腺素耗竭并用氟哌啶醇激发的损伤大鼠中也观察到多巴胺增加。这与未损伤对照组中氟哌啶醇对皮质多巴胺无影响形成对比。这些结果表明，去甲肾上腺素终末通过去甲肾上腺素转运体对多巴胺的摄取来调节内侧前额叶皮质以及程度较轻的伏隔核壳部的细胞外多巴胺浓度。
