Savaki H E, Raos V C, Dermon C R
Department of Basic Sciences, School of Health Sciences, University of Crete, Iraklion, Greece.
Neuroscience. 1992 Oct;50(4):781-94. doi: 10.1016/0306-4522(92)90204-f.
Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D[1-14C]glucose technique in the rat brain in order to determine the metabolic effects of unilateral intranigral application of the GABAA agonist muscimol upon the substantia nigra and its targets. Intranigral injection of 1.5 microliters 0.3 M muscimol (52 micrograms total dose) induced local metabolic activation in the injected substantia nigra reticulata (by 87% as compared to the control group), and distal metabolic depressions in the nucleus accumbens, striatum, globus pallidus and subthalamic nucleus only ipsilaterally to the injected nigra. The remaining basal ganglia components, including the substantia nigra compacta and the entopeduncular nucleus were bilaterally unaffected. Among the principal efferent projections of the substantia nigra reticulata, the ventromedial and centrolateral thalamic nuclei as well as the deep layers of the superior colliculi were metabolically depressed bilaterally, whereas the ventrolateral, parafascicular and mediodorsal thalamic nuclei as well as the pedunculopontine nucleus displayed metabolic depressions ipsilateral to the muscimol-injection nigra. The ventromedial and centrolateral thalamic nuclei were depressed by 41 and 42%, respectively, in the ipsilateral side, and by 30 and 26% in the contralateral side, when compared to the respective values of the control group of rats. Furthermore, unilateral intranigral injection of 0.3 M muscimol induced metabolic depressions in reticular, intralaminar and prefrontal thalamocortical areas mostly ipsilateral to the injected nigra, as well as in limbic areas bilaterally. It is suggested that the present findings are due to a postsynaptic effect of muscimol on the nigral GABAergic cells and to a consequent metabolic depression of the basal ganglia and associated thalamocortical areas, in contrast to an earlier suggested presynaptic nigral effect of lower doses of intranigrally injected muscimol which induced metabolic activations within the same network. This suggestion is further supported by the fact that intranigrally injected substrate P19 induced similar effects to those elicited by the lower doses of intranigral muscimol and opposite to those induced at present by the higher muscimol dose. Moreover, it is further substantiated that the nigrothalamic GABAergic system is responsible for considerable transfer of information from one substantia nigra reticulata to the ipsilateral basal ganglia and associated thalamocortical components as well as to bilateral motor, intralaminar and limbic areas.
为了确定GABAA激动剂蝇蕈醇单侧黑质内注射对黑质及其靶点的代谢影响，采用放射自显影2-脱氧-D[1-14C]葡萄糖技术测量大鼠脑内的脑葡萄糖利用率。向黑质内注射1.5微升0.3M蝇蕈醇（总剂量52微克）可诱导注射侧黑质网状部局部代谢激活（与对照组相比增加87%），并且仅在注射侧黑质同侧的伏隔核、纹状体、苍白球和丘脑底核出现远隔代谢抑制。其余基底神经节成分，包括黑质致密部和内囊核，双侧均未受影响。在黑质网状部的主要传出投射中，腹内侧和中央外侧丘脑核以及上丘深层出现双侧代谢抑制，而腹外侧、束旁和背内侧丘脑核以及脚桥核在注射蝇蕈醇侧的黑质同侧出现代谢抑制。与对照组大鼠的相应值相比，腹内侧和中央外侧丘脑核在同侧分别降低41%和42%，在对侧分别降低30%和26%。此外，单侧黑质内注射0.3M蝇蕈醇可诱导主要在注射侧黑质同侧的网状、板内和前额叶丘脑皮质区以及双侧边缘区出现代谢抑制。提示目前的发现是由于蝇蕈醇对黑质GABA能细胞的突触后作用以及随后基底神经节和相关丘脑皮质区的代谢抑制，这与早期提出的较低剂量黑质内注射蝇蕈醇的突触前黑质作用相反，后者在同一网络内诱导代谢激活。向黑质内注射底物P19诱导的效应与较低剂量黑质内注射蝇蕈醇诱导的效应相似，与目前较高剂量蝇蕈醇诱导的效应相反，这一事实进一步支持了这一观点。此外，进一步证实黑质-丘脑GABA能系统负责将大量信息从一侧黑质网状部传递到同侧基底神经节和相关丘脑皮质成分以及双侧运动、板内和边缘区。
