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

• Published in: Neuroscience 1999-03, Vol.89 (3), p.827-837
• Main Authors: Svenningsson, P, Fourreau, L, Bloch, B, Fredholm, B.B, Gonon, F, Le Moine, C
• Format: Article
• Language: English
• Subjects: Adenosine - physiology; adenosine A 2A receptors; Animals; Antiparkinson Agents - pharmacology; Biological and medical sciences; c- fos mRNA; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - physiology; Dopamine Agonists - pharmacology; dopamine D 2 receptors; dopamine release; Drug Design; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes, fos - drug effects; Globus Pallidus - drug effects; Globus Pallidus - metabolism; In Situ Hybridization; Life Sciences; Male; Medicin och hälsovetenskap; Models, Neurological; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurons - drug effects; Neurons - metabolism; Neurons and Cognition; Oxidopamine - toxicity; Proto-Oncogene Proteins c-fos - biosynthesis; Purinergic P1 Receptor Antagonists; Pyrimidines - pharmacology; Quinolines - pharmacology; Rats; Rats, Wistar; Receptor, Adenosine A2A; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - biosynthesis; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - physiology; RNA, Messenger - biosynthesis; striatum; Triazoles - pharmacology; Tyrosine 3-Monooxygenase - biosynthesis; Tyrosine 3-Monooxygenase - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00403-5

The impulse flow-dependent dopamine release in the striatum was acutely blocked by unilateral lesion of the medial forebrain bundle with 6-hydroxydopamine. Within 45 min this disruption reduced the striatal extracellular dopamine levels by 80% as determined by in vivo voltammetry. A strong induction of c- fos messenger RNA was detected in the ipsilateral dorsolateral striatum 75 min after 6-hydroxydopamine injection by in situ hybridization. Double labelling demonstrates that this induction was confined to neurons expressing the dopamine D 2 receptor messenger RNA. At this time-point, there were no changes in the striatal levels of either tyrosine hydroxylase immunoreactivity or dopamine D 2 receptor messenger RNA. The c- fos messenger RNA expression induced by acute 6-hydroxydopamine injection was abolished by intraperitoneal pretreatment with the dopamine D 2 receptor agonist, quinelorane (2 mg/kg) and strongly reduced by administration of the selective adenosine A 2A receptor antagonist SCH-58261 (5 mg/kg). The results reported here show, by using a novel methodological approach, that an acute decrease of dopamine release causes an induction of c- fos messenger RNA in dopamine D 2 receptor-containing striatopallidal neurons. This, together with previous findings, demonstrates that the c- fos gene expression is tonically inhibited by the impulse flow-dependent dopamine release via D 2 receptors. In addition, this study provides evidence that endogenous adenosine, acting via adenosine A 2A receptors, induces striatal c- fos messenger RNA when extracellular dopamine levels are strongly reduced. Thus endogenous dopamine and adenosine exert opposite effects on the activity of the D 2-containing striatopallidal neurons.