Compartmental changes in expression of c-Fos and FosB proteins in intact and dopamine-depleted striatum after chronic apomorphine treatment.
Chronic administration of dopaminergic agonists to rats with unilateral 6-OH-dopamine (6-OHDA) lesions of nigrostriatal pathway produces behavioral sensitization to subsequent agonist challenges and may serve as a model for DOPA-induced dyskinesias. In order to understand striatal mechanisms behind this long-term behavioral change we examined striatal c-Fos and FosB immunoreactivity induced by apomorphine challenge (5 mg/kg, s.c.) after 3 days of withdrawal following a 2-week administration (5 mg/kg, b.i.d., s.c.) both in intact and 6-OHDA-lesioned animals. In intact rats, c-Fos induction by acute apomorphine exposure showed a striosomal pattern, whereas FosB immunopositivity was diffusely distributed. Following chronic administration, FosB induction turned to a clear striosome dominant pattern similar to c-Fos expression. In denervated striatum, expression of both proteins was profoundly augmented in a homogeneous pattern after a single dose of apomorphine. A distinct striosomal patterning appeared after chronic apomorphine administration in ventromedial part of the denervated striatum with a down-regulation in the matrix and relative enhancement in striosomes. These results suggest that compartmental reorganization of striatal neuronal activity may play a role in long-term behavioral changes induced by chronic dopaminergic treatments both under normal and dopamine-depleted conditions.
Saka
E
E
Department of Neurology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.
Elibol
B
B
Erdem
S
S
Dalkara
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D064026:Calbindins; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D003714:Denervation; D004298:Dopamine / Q000172:deficiency*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009473:Neuronal Plasticity / Q000502:physiology; D016627:Oxidopamine; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D013565:Sympatholytics
D064026:Calbindins; D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D064030:S100 Calcium Binding Protein G; D013565:Sympatholytics; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine