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Metabolic mapping of the synergism between MK‐801 and SKF 38393 in rats with unilateral lesions of the dopaminergic nigrostriatal pathway
Author(s) -
Pontieri Francesco E.,
Morelli Micaela,
Orzi Francesco,
Terenzi Riccardo,
Di Chira Gaetano
Publication year - 1992
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890120402
Subject(s) - agonist , substantia nigra , nigrostriatal pathway , dopaminergic , stimulation , medicine , chemistry , endocrinology , lesion , habenula , oxidopamine , dopamine , pharmacology , neuroscience , receptor , psychology , central nervous system , psychiatry
In rats with a unilateral lesion of the dopaminergic nigrostriatal pathway with 6‐hydroxydopamine, blockade of N‐methyl‐D‐aspartate receptors by MK‐801 strongly potentiated the turning behavior induced by D‐1 receptor stimulation. To determine the functional consequences of such positive interaction we measured the local rates of cerebral glucose utilization (ICMR glc ) in lesioned rats treated with MK‐801 (0.1mg/kg) and the D‐1 agonist SKF 38393 (1.5 mg/kg), either alone or in combination. Treatment with each drug separately did not induce any substantial change in ICMR glc besides an increase in the metabolic activity of the dorsomedial caudate and entopeduncular nucleus (EP) of the lesioned side of MK‐801 treated rats, as compared to the same side of lesioned rats treated with vehicle. Combined administration of MK‐801 + SKF 38393 increased ICMR glc in the EP (+77%) and in the substantia nigra pars reticulata (SNr) (+30%) of the lesioned side as compared with the intact side, while it decreased ICMR glc in the lateral habenula (−26%). These changes were also significant when compared to the lesioned side of vehicle treated rats. The results suggest that while the caudate putamen might be the primary site of MK‐801 and SKF 38393 positive interaction, the EP and SNr are the striatal efferent areas where this positive interaction is expressed. © 1992 Wiley‐Liss, Inc.