Opposite tonic modulation of dopamine and adenosine on c-fos gene expression in striatopallidal neurons

The impulse flow-dependent dopamine release in the striatum was acutely blo cked by unilateral lesion of the medial forebrain bundle with 6-hydroxydopa mine. Within 45 min this disruption reduced the striatal extracellular dopa mine levels by 80% as determined by in vivo voltammetry. A strong induction of c-fos messenger RNA was detected in the ipsilateral dorsolateral striat um 75min after 6-hydroxydopamine injection by in situ hybridization. Double labelling demonstrates that this induction was confined to neurons express ing the dopamine D-2 receptor messenger RNA. At this time-point, there were no changes in the striatal levels of either tyrosine hydroxylase immunorea ctivity or dopamine D-2 receptor messenger RNA. The c-fos messenger RNA exp ression induced by acute 6-hydroxydopamine injection was abolished by intra peritoneal pretreatment with the dopamine D2 receptor agonist, quinelorane (2 mg/kg) and strongly reduced by administration of the selective adenosine A,, receptor antagonist SCH-58261 (5 mg/kg). The results reported here show, by using a novel methodological approach, t hat an acute decrease of dopamine release causes an induction of c-fos mess enger RNA in dopamine D-2 receptor-containing striatopallidal neurons. This , together with previous findings, demonstrates that the c-fos gene express ion is tonically inhibited by the impulse flow-dependent dopamine release v ia D-2 receptors. In addition, this study provides evidence that endogenous adenosine, acting via adenosine A,receptors, induces striatal c-fos messen ger RNA when extracellular dopamine levels are strongly reduced. Thus endog enous dopamine and adenosine exert opposite effects on the activity of the D-2-containing striatopallidal neurons. (C) 1999 IBRO. Published by Elsevie r Science Ltd.