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Local cerebral glucose utilization after D1 receptor stimulation in 6‐OHDA lesioned rats: Effect of sensitization (priming) with a dopaminergic agonist
Author(s) -
Morelli Micaela,
Pontieri Francesco E.,
Linfante Italo,
Orzi Francesco,
Di Chiara Gaetano
Publication year - 1993
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.890130309
Subject(s) - agonist , chemistry , dopaminergic , lesion , medicine , endocrinology , stimulation , sensitization , globus pallidus , oxidopamine , pharmacology , dopamine , substantia nigra , basal ganglia , receptor , neuroscience , central nervous system , psychology , psychiatry
Abstract In rats bearing unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the dopaminergic nigro‐striatal neurons, a single administration of a D‐2 agonist (LY 17155) potentiates the contralateral turning induced by a D‐1 agonist (SKF 38393). To identify the neural substrate of this form of sensitization (priming), we studied the local cerebral glucose utilization (lCMR glc ) in 6‐OHDA lesioned animals treated, 3 days apart, as follows: (1) saline‐saline, (2) LY 171555‐saline, (3) saline‐SKF 38393 and (4) LY 171555‐SKF 38393. The unilateral 6‐OHDA lesion per se (Sal‐Sal) produced increases in lCMR glc in the globus pallidus (GP) and in the lateral habenula (LH) of the lesioned hemisphere. lCMR glc in LY‐Sal group were similar to those measured in the Sal‐Sal group. Administration of SKF 38393 to drug‐naïve rats (Sal‐SKF) abolished the lesion‐induced metabolic asymmetry in the LH but did not have any effect on the GP; furthermore, it increased lCMR glc in the substantia nigra pars reticulata (SNr) of the lesioned side. After priming with LY 171555, administration of SKF 38393 (LY‐SKF) produced marked metabolic asymmetries by increasing lCMR glc in the SNr and entopeduncular nucleus (EP), and decreasing it in the LH of the lesioned side. These changes were also significant when compared to the corresponding values of the other experimental groups. Again, in LY‐SKF group no modification of the lesion‐induced metabolic asymmetry in the GP was found. These results indicate that priming exerts a facilitatory influence on the ability of D‐1 receptors to stimulate the striato‐nigral and striato‐entopeduncular pathway, suggesting that changes in the effectiveness of dopamine in activating its postsynaptic target elements might contribute to the mechanism of sensitization to drugs stimulating dopaminergic transmission. © 1993 Wiley‐Liss, Inc.