Morari M, O'Connor W T, Ungerstedt U, Bianchi C, Fuxe K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1996 May;72(1):89-97. doi: 10.1016/0306-4522(95)00556-0.
In the present study we used the dual probe approach to investigate striatal N-methyl-D-aspartate receptor regulation of GABA release from the substantia nigra pars reticulata of the awake, freely moving rat. One microdialysis probe of concentric design was implanted in the dorsolateral striatum and another in the ipsilateral substantia nigra pars reticulata. Perfusion with N-methyl-D-aspartate (100 microM) in the dorsolateral striatum decreased local dopamine release (-25%) and increased both glutamate (+40%) and GABA (+35%) release. Moreover, perfusion with N-methyl-D-aspartate (100 microM) in the dorsolateral striatum increased GABA release (+20%) in the substantia nigra pars reticulata. Perfusion with the lower (10 microM) N-methyl-D-aspartate concentration in the dorsolateral striatum did not affect striatal dopamine, glutamate and GABA release or nigral GABA release. Intrastriatal perfusion with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (10 microM), at a dose which by itself did not affect basal striatal or nigral neurotransmitter levels, prevented the effects of striatal perfusion with N-methyl-D-aspartate on both striatal and nigral neurotransmitter release. Intrastriatal dizocilpine maleate was also perfused concurrently with intranigral tetrodotoxin (10 microM) (see accompanying paper). Intrastriatal perfusion with dizocilpine maleate prevented the tetrodotoxin-induced rise in both striatal and nigral GABA levels and profoundly reduced the tetrodotoxin-induced contralateral turning. In addition, intrastriatal dizocilpine maleate delayed the increase in striatal glutamate release evoked by intranigral tetrodotoxin without affecting the associated decrease in striatal dopamine release. The present study demonstrates that N-methyl-D-aspartate receptors in the dorsolateral striatum regulate GABA release in the substantia nigra pars reticulata of the awake rat and provides evidence that this regulation plays a key role in motor function.
在本研究中，我们采用双探针方法来研究清醒、自由活动大鼠黑质网状部中纹状体N-甲基-D-天冬氨酸受体对γ-氨基丁酸（GABA）释放的调节作用。一个同心设计的微透析探针植入背外侧纹状体，另一个植入同侧黑质网状部。向背外侧纹状体灌注N-甲基-D-天冬氨酸（100微摩尔）可降低局部多巴胺释放（-25%），并增加谷氨酸（+40%）和GABA（+35%）的释放。此外，向背外侧纹状体灌注N-甲基-D-天冬氨酸（100微摩尔）可增加黑质网状部的GABA释放（+20%）。向背外侧纹状体灌注较低浓度（10微摩尔）的N-甲基-D-天冬氨酸不影响纹状体多巴胺、谷氨酸和GABA的释放，也不影响黑质GABA的释放。向纹状体内灌注N-甲基-D-天冬氨酸受体拮抗剂马来酸氯氮平（10微摩尔），该剂量本身不影响基础纹状体或黑质神经递质水平，可阻止纹状体灌注N-甲基-D-天冬氨酸对纹状体和黑质神经递质释放的影响。纹状体内的马来酸氯氮平也与黑质内的河豚毒素（10微摩尔）同时灌注（见随附论文）。纹状体内灌注马来酸氯氮平可阻止河豚毒素诱导的纹状体和黑质GABA水平升高，并显著降低河豚毒素诱导的对侧旋转。此外，纹状体内灌注马来酸氯氮平可延迟黑质内河豚毒素诱发的纹状体谷氨酸释放增加，而不影响纹状体多巴胺释放的相关减少。本研究表明，背外侧纹状体中的N-甲基-D-天冬氨酸受体调节清醒大鼠黑质网状部中的GABA释放，并提供证据表明这种调节在运动功能中起关键作用。
