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-binding 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 the lateral caudate-putamen of rats treated acutely and chronically with the D2 receptor antagonist fluphenazine (phenothiozine typical psychotic). To determine whether D1 receptor stimulation is also capable of inducing CArG-binding protein A up-regulation, drug naive or dopamine-depleted (i.e. 6-hydroxydopamine-lesioned) D1 hypersensitized rats (i.e. rats given repeated daily injections of SKF-82958 for 14days) 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 increases in CArG-binding protein A. Moderate increases were found in the medial caudate-putamen and nucleus accumbens core and shell regions following acute treatment whereas large increases in CArG-binding protein A expression levels were found in the medial and lateral caudate-putamen and the shell and 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 where increases in CArG-binding protein A were detected following each treatment correlated perfectly with c-Fos protein induction. The results demonstrate that CArG-binding protein A responds to SKF-82958 and that the changes in CArG-binding protein A match perfectly with the pattern of c-Fos induction induced by the D1 agonist.