Carboni E, Tanda G L, Frau R, Di Chiara G
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
J Neurochem. 1990 Sep;55(3):1067-70. doi: 10.1111/j.1471-4159.1990.tb04599.x.
The effect of systemic administration of desmethylimipramine (DMI) and oxaproptiline (OXA), two inhibitors of the noradrenaline (NA) reuptake carrier, on the in vivo extracellular concentrations of dopamine (DA) was studied by transcerebral dialysis in the prefrontal cortex and in the dorsal caudate of freely moving rats. In the NA-rich prefrontal cortex, either drug increased extracellular DA concentrations whereas in the dorsal caudate neither was effective. Haloperidol increased extracellular DA concentrations more effectively in the dorsal caudate than in the prefrontal cortex. Pre-treatment with DMI or OXA, which failed to modify the effect of haloperidol in the dorsal caudate, potentiated its action in the prefrontal cortex. 6-Hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of OXA to increase DA concentrations. The results suggest that reuptake into NA terminals in an important mechanism by which DA is cleared from the extracellular space in a NA-rich area such as the prefrontal cortex. The elevated extracellular concentrations of DA resulting from blockade of such mechanism by tricyclic antidepressants may play a role in the therapeutic effects of these drugs.
通过对自由活动大鼠的前额叶皮质和背侧尾状核进行脑透析，研究了去甲丙咪嗪（DMI）和奥沙普替林（OXA）这两种去甲肾上腺素（NA）再摄取载体抑制剂经全身给药后对多巴胺（DA）体内细胞外浓度的影响。在富含NA的前额叶皮质中，两种药物均可提高细胞外DA浓度，而在背侧尾状核中则均无效。氟哌啶醇在背侧尾状核中比在前额叶皮质中更有效地提高细胞外DA浓度。预先用DMI或OXA处理，虽然未能改变氟哌啶醇在背侧尾状核中的作用，但增强了其在前额叶皮质中的作用。对背侧NA束进行6-羟基多巴胺损伤可阻止OXA提高DA浓度的能力。结果表明，再摄取进入NA终末是DA从富含NA的区域（如前额叶皮质）的细胞外空间清除的重要机制。三环类抗抑郁药阻断这种机制导致细胞外DA浓度升高，可能在这些药物的治疗作用中发挥作用。
