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-O H-dopamine (6-OHDA) lesions of nigrostriatal pathway produces behavioral se nsitization to subsequent agonist challenges and may serve as a model for D OPA-induced dyskinesias. In order to understand striatal mechanisms behind this long-term behavioral change we examined striatal c-Fos and FosB immuno reactivity 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 a cute apomorphine exposure showed a striosomal pattern, whereas FosB immunop ositivity was diffusely distributed. Following chronic administration, FosB induction turned to a clear striosome dominant pattern similar to c-Fos ex pression. In denervated striatum, expression of both proteins was profoundl y augmented in a homogeneous pattern after a single dose of apomorphine. A distinct striosomal patterning appeared after chronic apomorphine administr ation in ventromedial part of the denervated striatum with a down-regulatio n in the matrix and relative enhancement in striosomes. These results sugge st that compartmental reorganization of striatal neuronal activity may play a role in long-term behavioral changes induced by chronic dopaminergic tre atments both under normal and dopamine-depleted conditions. (C) 1999 Elsevi er Science B.V. All rights reserved.