Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABAA receptor agonist muscimol

Abstract

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.