Gong W, Neill D, Justice J B
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Brain Res. 1997 Apr 18;754(1-2):103-12. doi: 10.1016/s0006-8993(97)00059-0.
In parallel with nucleus accumbens (NAS), ventral pallidum (VP) also receives a dopaminergic projection from the ventral tegmental area (VTA). The present study examined the involvement of this mesopallidal dopaminergic system in the action of cocaine. In the first experiment, the effect of cocaine injections on VP dopamine was examined by microdialysis. Intraperitoneal (i.p.) injections of cocaine 5-20 mg/kg dose-dependently increased the extracellular dopamine level in VP 2.5-4.5-fold. In addition, intra-VP perfusion of 20 microM cocaine induced a 12-fold increase of dopamine locally. The second experiment examined the role of VP dopamine in cocaine-induced conditioned place preference (CPP) and locomotor activation. Rats received bilateral intra-VP injections of 3-4 microg 6-OHDA or ascorbic acid vehicle in 0.5 microl volume. Tissue assays indicated that the 6-OHDA-lesioned rats had significantly lowered dopamine concentration in VP, but not in NAS or striatum. As a group, 6-OHDA lesions blocked the development of CPP to 5 mg/kg cocaine but not to 10 mg/kg cocaine. However, rats with more than 60% depletion in VP dopamine did not develop CPP to cocaine at either dose. Preference for the cocaine-paired side correlated significantly with dopamine concentration in VP, but not in NAS or striatum. It was concluded that VP dopamine may play a critical role in the initial rewarding effect of cocaine. 6-OHDA lesions also blocked locomotor activation induced by 5 mg/kg cocaine but had no effect on 10 mg/kg cocaine-induced locomotion. Dopamine concentration in VP did not correlate with the locomotor activation response to cocaine at either dose. These findings further establish the involvement of the mesopallidal dopaminergic system in the action of cocaine.
与伏隔核（NAS）一样，腹侧苍白球（VP）也接受来自腹侧被盖区（VTA）的多巴胺能投射。本研究考察了这条中脑苍白球多巴胺能系统在可卡因作用中的参与情况。在第一个实验中，通过微透析检测了可卡因注射对VP区多巴胺的影响。腹腔注射5 - 20 mg/kg可卡因可使VP区细胞外多巴胺水平呈剂量依赖性升高2.5 - 4.5倍。此外，向VP区内灌注20 μM可卡因可使局部多巴胺水平升高12倍。第二个实验考察了VP区多巴胺在可卡因诱导的条件性位置偏爱（CPP）和运动激活中的作用。大鼠双侧VP区内注射3 - 4 μg 6 - 羟基多巴胺（6 - OHDA）或0.5 μl体积的抗坏血酸载体。组织检测表明，6 - OHDA损伤的大鼠VP区多巴胺浓度显著降低，但NAS区或纹状体中多巴胺浓度未降低。作为一个整体，6 - OHDA损伤阻断了对5 mg/kg可卡因的CPP形成，但未阻断对10 mg/kg可卡因的CPP形成。然而，VP区多巴胺耗竭超过60%的大鼠对两种剂量的可卡因均未形成CPP。对可卡因配对侧的偏爱与VP区多巴胺浓度显著相关，但与NAS区或纹状体中的多巴胺浓度无关。研究得出结论，VP区多巴胺可能在可卡因的初始奖赏效应中起关键作用。6 - OHDA损伤也阻断了5 mg/kg可卡因诱导的运动激活，但对10 mg/kg可卡因诱导的运动无影响。两种剂量下，VP区多巴胺浓度与对可卡因的运动激活反应均无相关性。这些发现进一步证实了中脑苍白球多巴胺能系统参与了可卡因的作用。
