Di Chiara G, Tanda G L, Frau R, Carboni E
Institute of Experimental Pharmacology & Toxicology, University of Cagliari, Italy.
Neurochem Int. 1992 Mar;20 Suppl:231S-235S.
The effect of systemic administration of desmethylimipramine (DMI), an inhibitor of the noradrenaline (NA) reuptake carrier, and of GBR 12909, an inhibitor of the dopamine (DA) 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 only DMI increased extracellular DA concentrations whereas in the dorsal caudate only GBR 12909 was effective. Haloperidol increased extracellular DA concentrations more effectively in the dorsal caudate than in the prefrontal cortex. Pretreatment with DMI, which failed to modify the effect of haloperidol in the dorsal caudate, potentiated its action in the prefrontal cortex. The reverse was obtained after GBR 12909+ haloperidol in the two areas. 6-hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of DMI to increase DA concentrations. The results suggest that reuptake into NA terminals is 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，研究了去甲肾上腺素（NA）再摄取载体抑制剂去甲丙咪嗪（DMI）和多巴胺（DA）再摄取载体抑制剂GBR 12909全身给药对体内多巴胺（DA）细胞外浓度的影响。在富含NA的前额叶皮质中，只有DMI增加了细胞外DA浓度；而在背侧尾状核中，只有GBR 12909有效。氟哌啶醇在背侧尾状核中比在前额叶皮质中更有效地增加细胞外DA浓度。预先用DMI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。在两个区域给予GBR 12909 +氟哌啶醇后，结果相反。对背侧NA束进行6-羟基多巴胺损伤可阻止DMI增加DA浓度的能力。结果表明，再摄取进入NA终末是在富含NA的区域（如前额叶皮质）中DA从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的细胞外DA浓度升高可能在这些药物的治疗作用中发挥作用。
