Maeda T, Kannari K, Suda T, Matsunaga M
Department of Neurology, Institute of Neurological Diseases, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8216, Japan.
Brain Res. 1999 Jan 30;817(1-2):185-91. doi: 10.1016/s0006-8993(98)01248-7.
To determine whether dopamine release derived from exogenous l-DOPA is under inhibitory control of presynaptic dopamine D2 receptors in the dopaminergic denervated striatum, extracellular dopamine levels were measured in the striatum of 6-hydroxydopamine-lesioned rats using in vivo brain microdialysis. Quinpirole, a D2 agonist, dose-dependently (0.01-3 mg/kg s.c.) inhibited endogenous dopamine release both in the intact and dopaminergic denervated striatum. The dose-response curve obtained from the denervated striatum showed a shift to the right. Administration of l-DOPA (30 mg/kg i.p.) with carbidopa (25 mg/kg i.p.) increased dopamine release to 130% of basal levels in the intact striatum and 770% of basal levels in the denervated striatum. In the intact striatum, dopamine release was continuously inhibited by quinpirole pretreatment (1 mg/kg s.c.) even after l-DOPA administration. In the denervated striatum, l-DOPA-derived dopamine release was not affected by quinpirole pretreatment. These results suggest that, in the striatum with dopaminergic denervation, regulation by presynaptic D2 receptors is still operative on endogenous dopamine release but it does not work on dopamine release derived from exogenously administered l-DOPA.
为了确定外源性左旋多巴释放的多巴胺是否受多巴胺能去神经支配纹状体中突触前多巴胺D2受体的抑制性控制，使用体内脑微透析法测量了6-羟基多巴胺损伤大鼠纹状体中的细胞外多巴胺水平。D2激动剂喹吡罗以剂量依赖性方式（0.01-3mg/kg皮下注射）抑制完整和多巴胺能去神经支配纹状体中的内源性多巴胺释放。从去神经支配纹状体获得的剂量反应曲线向右移动。左旋多巴（30mg/kg腹腔注射）与卡比多巴（25mg/kg腹腔注射）联合给药使完整纹状体中的多巴胺释放增加至基础水平的130%，使去神经支配纹状体中的多巴胺释放增加至基础水平的770%。在完整纹状体中，即使在给予左旋多巴后，喹吡罗预处理（1mg/kg皮下注射）也能持续抑制多巴胺释放。在去神经支配纹状体中，左旋多巴衍生的多巴胺释放不受喹吡罗预处理的影响。这些结果表明，在多巴胺能去神经支配的纹状体中，突触前D2受体的调节对内源性多巴胺释放仍然有效，但对外源性给予的左旋多巴释放的多巴胺不起作用。
