Morari M, O'Connor W T, Darvelid M, Ungerstedt U, Bianchi C, Fuxe K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1996 May;72(1):79-87. doi: 10.1016/0306-4522(95)00557-9.
In the present study we employed the dual probe approach to investigate functional interactions between the nigrostriatal dopaminergic and striatonigral GABAergic pathways in the awake, freely moving rat and their role in motor function. One microdialysis probe of concentric design was implanted in the substantia nigra pars reticulata and another in the ipsilateral dorsolateral striatum. Perfusion with a low-Ca2+ (0.1 mM) medium and with the voltage-dependent Na(+)-channel blocker tetrodotoxin (10 microM) was alternatively performed in both brain regions and the dialysate dopamine, glutamate and GABA levels were simultaneously measured in the dorsolateral striatum, whereas GABA levels alone were monitored in the substantia nigra. Perfusion with a low-Ca2+ medium in the substantia nigra pars reticulata did not affect local GABA levels, but transiently increased striatal dopamine release (+40%) without modifying striatal glutamate and GABA levels. Conversely, intranigral perfusion with tetrodotoxin transiently increased local GABA levels (+40%), while it decreased striatal dopamine (-60%) and increased glutamate (+70%) and GABA (+50%) levels. Perfusion with a low-Ca2+ medium in the dorsolateral striatum reversibly decreased local dopamine (-70%), glutamate (-20%) and GABA (-20%) levels, while local perfusion with tetrodotoxin decreased dopamine (-70%), increased glutamate (+30%) but did not affect dialysate GABA levels in this brain area. Neither of these intrastriatal treatments significantly affected GABA levels in the substantia nigra. Intranigral but not intrastriatal perfusion with tetrodotoxin was also associated with an increase in spontaneous locomotor activity as expressed by contralateral turning. Intranigral and intrastriatal perfusion with low-Ca2+ medium did not influence locomotor activity. On the basis of these neurochemical and behavioural findings, we propose a new dynamic model for the study of motor behaviour as mediated by basal ganglia circuitry.
在本研究中，我们采用双探针方法来研究清醒、自由活动大鼠中黑质纹状体多巴胺能通路与纹状体黑质γ-氨基丁酸（GABA）能通路之间的功能相互作用及其在运动功能中的作用。一个同心设计的微透析探针植入黑质网状部，另一个植入同侧背外侧纹状体。在两个脑区交替灌注低钙（0.1 mM）培养基和电压依赖性钠通道阻滞剂河豚毒素（10 μM），同时测量背外侧纹状体中的透析液多巴胺、谷氨酸和GABA水平，而仅监测黑质中的GABA水平。黑质网状部灌注低钙培养基不影响局部GABA水平，但可短暂增加纹状体多巴胺释放（增加40%），而不改变纹状体谷氨酸和GABA水平。相反，黑质内灌注河豚毒素可短暂增加局部GABA水平（增加40%），同时降低纹状体多巴胺（降低60%），增加谷氨酸（增加70%）和GABA（增加50%）水平。背外侧纹状体灌注低钙培养基可逆性降低局部多巴胺（降低70%）、谷氨酸（降低20%）和GABA（降低20%）水平，而局部灌注河豚毒素可降低多巴胺（降低70%），增加谷氨酸（增加30%），但不影响该脑区的透析液GABA水平。这些纹状体内处理均未显著影响黑质中的GABA水平。黑质内而非纹状体内灌注河豚毒素还与对侧旋转所表达的自发运动活动增加有关。黑质内和纹状体内灌注低钙培养基不影响运动活动。基于这些神经化学和行为学发现，我们提出了一个由基底神经节回路介导运动行为研究的新动态模型。
