Hebert M A, Van Horne C G, Hoffer B J, Gerhardt G A
Neuroscience Training Program, University of Colorado Health Sciences Center Denver, USA.
J Pharmacol Exp Ther. 1996 Dec;279(3):1181-90.
The functional effects of a single dual-site intranigral administration (10 micrograms) of glial cell line-derived neurotrophic factor (GDNF) on dopamine (DA) neurons in the basal ganglia of young Fischer 344 rats were investigated. A combination of behavioral, in vivo electrochemical, microdialysis and high-performance liquid chromatography methods were used to study the effects of this novel peptide. Behaviorally, significant changes in spontaneous locomotor activity were found 1 week, but not 3 weeks, after GDNF treatment. However, the velocity of movements was increased in the GDNF-treated animals 3 weeks after GDNF administration, a result that corresponded to significant enhancement of stimulus-evoked release of DA. Two-fold increases in potassium-evoked DA overflow were seen throughout the striatum by means of high-speed chronoamperometry 3 weeks after GDNF injection. No significant change in basal levels of DA was measured by microdialysis, although both potassium-evoked and d-amphetamine-induced DA overflow were significantly increased 3 weeks after treatment. Finally, significant changes in whole-tissue levels of DA were seen in the substantia nigra 1 week, but not 3 weeks, after GDNF administration. These data represent the first studies demonstrating that GDNF has long-lasting functional presynaptic effects on DA-containing neurons in the rat striatum.
研究了在年轻的Fischer 344大鼠基底神经节中单次双侧黑质内注射（10微克）胶质细胞源性神经营养因子（GDNF）对多巴胺（DA）神经元的功能影响。采用行为学、体内电化学、微透析和高效液相色谱等方法相结合，研究这种新型肽的作用。行为学上，GDNF治疗后1周发现自发运动活动有显著变化，但3周后未发现。然而，GDNF给药3周后，GDNF治疗组动物的运动速度增加，这一结果与刺激诱发的DA释放显著增强相对应。GDNF注射3周后，通过高速计时电流法在整个纹状体中观察到钾诱发的DA溢出增加了两倍。微透析测量未发现DA基础水平有显著变化，尽管治疗3周后钾诱发和d-苯丙胺诱导的DA溢出均显著增加。最后，GDNF给药后1周在黑质中观察到DA全组织水平有显著变化，但3周后未观察到。这些数据代表了首次证明GDNF对大鼠纹状体中含DA神经元具有持久的功能性突触前作用的研究。
