Changes in CArG-binding protein A expression levels following injection(s)of the D1-dopamine agonist SKF-82958 in the intact and 6-hydroxydopamine-lesioned rat

We recently characterized the rat brain homolog of mouse muscle CArG-bindin g protein A initially identified in C2 myogenic cells and showed an inverse temporal correlation between increased expression levels of this messenger RNA, c-fos and zif268 messenger RNA levels following the addition of nerve growth factor to PC12 cells. In addition, we found an inverse correlation between c-Fos protein and CArG-binding protein A messenger RNA levels in th e lateral caudate-putamen of rats treated acutely and chronically with the D2 receptor antagonist fluphenazine (phenothiozine typical psychotic). To d etermine whether D1 receptor stimulation is also capable of inducing CArG-b inding protein A up-regulation, drug naive or dopamine-depleted (i.e. 6-hyd roxydopamine-lesioned) D1 hypersensitized rats (i.e. rats given repeated da ily injections of SKF-82958 for 14 days) were acutely injected with the D1 agonist SKF-82958 and examined using a combination of in situ hybridization for CArG binding protein A and immunocytochemistry for c-Fos. Both acutely treated animals and dopamine-depleted hypersensitized animals showed incre ases in CArG-binding protein A. Moderate increases were found in the medial caudate-putamen and nucleus accumbens core and shall regions following acu te treatment whereas large increases in CArG-binding protein A expression l evels were found in the medial acid lateral caudate-putamen and the shell a nd core of the nucleus accumbens following hypersensitization. No change in CArG-binding protein A expression level was found in the dopamine-depleted , drug naive animals relative to controls. Regions of the basal ganglia whe re increases in CArG-binding protein A were detected following each treatme nt correlated perfectly with c-Fos protein induction. The results demonstrate that CArG-binding protein A responds to SKF-82958 a nd that the changes in CArG-binding protein A match perfectly with the patt ern of c-Fos induction induced by the D1 agonist. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.