Journal of Neuroscience, Vol 10, 2861-2878, Copyright © 1990 by Society for Neuroscience
Bilateral alterations in local cerebral glucose utilization following intranigral application of the GABAergic agonist muscimol
CR Dermon, P Pizarro, P Georgopoulos and HE Savaki
Department of Basic Sciences, School of Health Sciences, University of Crete, Greece.
Rates of cerebral glucose utilization were measured by means of the
autoradiographic 2-deoxy-D-[1-14C] glucose technique in 70 anatomically
discrete central nervous structures in conscious awake rats following
unilateral intranigral application of the GABAergic agonist muscimol.
Intranigral injection of 1.3 microliters 1 microM muscimol (0.15 ng)
induced increases in glucose consumption locally in the substantia nigra
reticulata (by 87%), distally in the contralateral reticulata, red nucleus,
nucleus accumbens, and prefrontal cortex, and bilaterally in the pyriform
cortex, as compared to values in control animals. Intranigral injection of
1.3 microliters 1 mM muscimol (150 ng) effected a local metabolic
activation in the substantia nigra reticulata (by 111% compared to the
control group) and in compacta (by 18%), as well as a distal activation in
the contralateral reticulata (by 39%) and contralateral compacta (by 29%).
Beyond the structures affected by the lower dose, the higher dose of
muscimol elicited widespread bilateral increases in glucose metabolism in
the rat brain. Among the principal nigral reticulata efferent projections,
the deep superior colliculi displayed ipsilateral metabolic activation (by
30%), whereas the parafascicular, mediodorsal, and ventromedial thalamic
projecting areas, as well as the pedunculopontine nucleus, displayed
bilateral activations compared to the control animals. The ventromedial and
ventrolateral thalamic nuclei contralateral to the injected substantia
nigra reticulata were 20% activated compared to the ipsilateral homologous
structures and 30% activated compared to the control rats. The areas that
send afferent projections to the reticulata (globus pallidus,
entopeduncular and subthalamic nuclei) were mainly activated contralateral
to the injected reticulata compared to values for control animals. In
general, following intranigral muscimol (1 mM) injection, glucose
metabolism was activated to a larger extent on the side contralateral to
the injection than on the ipsilateral side. It is suggested that the
present findings are due to a presynaptic nigral effect of muscimol on the
GABAergic autoreceptors of the striatonigral terminals and to a consequent
disinhibition of the reticulata GABAergic output.