Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P.
The metabolic activity of several anatomically distinct brain areas was investigated by means of the quantitative autoradiographic 2-deoxy-D[1-14C]glucose method in awake rats following unilateral intranigral application of the putative excitatory neurotransmitter substance P. The primary goal was to determine the metabolic effects of substance P on the substantia nigra and its targets. Intranigral injection of 1 mM substance P (1.5 microliters) induced metabolic activation locally in the substantia nigra reticulata by 117% and substantia nigra compacta by 35%, as well as distally in the contralateral substantia nigra reticulata by 22% and contralateral substantia nigra compacta by 21%. All the basal ganglia components, the striatum, pallidum, entopeduncular, subthalamic nucleus and nucleus accumbens displayed bilateral metabolic activations after unilateral intranigral substance P injection. Among the principal reticulata efferent projections, the ventromedial, ventrolateral, parafascicular, mediodorsal and centrolateral thalamic nuclei, as well as the pedunculopontine nucleus displayed bilateral metabolic activations after intranigral substance P application. Moreover, unilateral intranigral substance P injection elicited metabolic activations in the thalamic and cortical components of the reticular, intralaminar, limbic and prefrontal systems, mostly bilateral. It is suggested that substance P applied into one substantia nigra reticulata activates the compacta nigrostriatal dopaminergic and the reticulata nigrothalamic GABAergic outputs inducing distal metabolic effects, similar to those elicited by unilateral nigral electrical stimulation [Savaki et al. (1983) J. comp. Neurol. 213, 46-65] and, opposite to several of those induced by intranigral injection of the inhibitory GABAA agonist muscimol [Savaki et al. (1992) Neuroscience 50, 781-794]. Furthermore, it is suggested that the ipsilateral basal ganglia effects induced by intranigral substance P application are mediated via both the compacta dopaminergic nigrostriatal projection and the reticulata GABAergic nigro-thalamocortico-striatal loop, whereas the contralateral basal ganglia and associated thalamocortical effects are due to the activation of the GABAergic reticulata efferents and are mediated via an interthalamic circuitry involving the motor, reticular and intralaminar thalamic nuclei.
D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D003847:Deoxyglucose; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism; D006651:Histocytochemistry; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D013788:Thalamus / Q000033:anatomy & histology / Q000378:metabolism
D013373:Substance P; D003847:Deoxyglucose; D005947:Glucose