Pan W H, Chen N H, Tsai F Y, Liao H Y
Institute of Pharmacology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Eur J Pharmacol. 1996 Dec 19;317(2-3):205-13. doi: 10.1016/s0014-2999(96)00724-8.
We evaluated the effects of local cocaine infusion into the A10 (ventral tegmental area), the cell body of the mesocorticolimbic dopaminergic pathway, on the extracellular concentrations of dopamine and norepinephrine in the medial prefrontal cortex, one of its terminal fields. A 1-ml Hamilton syringe was used to infuse a cocaine solution, either 20 or 200 microM, into the ventral tegmental area of anesthetized rats for 120 min through a microdialysis probe. The pure artificial cerebrospinal fluid (0 microM cocaine) infusion served as a control and a lidocaine (100 microM) infusion was administered to prevent the local anesthetic effect of cocaine. After intrategmental cocaine infusion (either 20 or 200 microM), extracellular dopamine and norepinephrine in the ventral tegmental area both increased significantly to a steady state level (208 +/- 42 and 148 +/- 23% for low dose and 220 +/- 24 and 150 +/- 15% for high dose). Simultaneously, the 200-microM cocaine infusion caused a significant decrease in extracellular dopamine (77 +/- 5%) but an increase in norepinephrine (140 +/- 6%) in the medial prefrontal cortex. The local anesthetic, lidocaine, produced no effects on the dopamine or norepinephrine output (neither in the ventral tegmental area nor in the medial prefrontal cortex). This study not only supports recent findings of an increase in extracellular dopamine and norepinephrine in the ventral tegmental area on intrategmental cocaine infusion, but also demonstrates that cocaine infused locally in the ventral tegmental area can decrease dopamine and increase norepinephrine at a remote terminal area (medial prefrontal cortex). Finally, the introduction rate of cocaine into the ventral tegmental area by retrograde microdialysis was found to be 0.83 ng/min for the low dose and 8.14 ng/min for the high dose.
我们评估了向中脑边缘多巴胺能通路的细胞体——A10（腹侧被盖区）局部注射可卡因，对其终末区域之一内侧前额叶皮质细胞外多巴胺和去甲肾上腺素浓度的影响。使用1毫升汉密尔顿注射器，通过微透析探针，将20或200微摩尔的可卡因溶液注入麻醉大鼠的腹侧被盖区，持续120分钟。注入纯人工脑脊液（0微摩尔可卡因）作为对照，并注入利多卡因（100微摩尔）以防止可卡因的局部麻醉作用。在向腹侧被盖区内注入可卡因（20或200微摩尔）后，腹侧被盖区内细胞外多巴胺和去甲肾上腺素均显著增加至稳态水平（低剂量时分别为208±42%和148±23%，高剂量时分别为220±24%和150±15%）。同时，注入200微摩尔可卡因导致内侧前额叶皮质细胞外多巴胺显著减少（77±5%），而去甲肾上腺素增加（140±6%）。局部麻醉药利多卡因对多巴胺或去甲肾上腺素的释放没有影响（在腹侧被盖区和内侧前额叶皮质均无影响）。本研究不仅支持了近期关于向腹侧被盖区内注入可卡因后腹侧被盖区内细胞外多巴胺和去甲肾上腺素增加的研究结果，还表明在腹侧被盖区局部注入可卡因可使远处终末区域（内侧前额叶皮质）的多巴胺减少、去甲肾上腺素增加。最后，通过逆行微透析发现，低剂量可卡因进入腹侧被盖区的速率为0.83纳克/分钟，高剂量为8.14纳克/分钟。
