title: Opposite tonic modulation of dopamine and adenosine on c-fos gene expression in striatopallidal neurons.
abstract: 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 D2 receptor messenger RNA. At this time-point, there were no changes in the striatal levels of either tyrosine hydroxylase immunoreactivity or dopamine D2 receptor messenger RNA. The c-fos messenger RNA expression induced by acute 6-hydroxydopamine injection was abolished by intraperitoneal pretreatment with the dopamine D2 receptor agonist, quinelorane (2 mg/kg) and strongly reduced by administration of the selective adenosine A2A 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 D2 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 D2 receptors. In addition, this study provides evidence that endogenous adenosine, acting via adenosine A2A 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 D2-containing striatopallidal neurons.
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors: P
authors: P
authors: Svenningsson
authors: L
authors: L
authors: Fourreau
authors: B
authors: B
authors: Bloch
authors: B B
authors: BB
authors: Fredholm
authors: F
authors: F
authors: Gonon
authors: C
authors: C
authors: Le Moine
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D011804:Quinolines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D014230:Triazoles; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D000241:Adenosine; D004298:Dopamine; C047726:quinelorane