Adenosine A2 receptors stimulate c-fos expression in striatal neurons of 6-hydroxydopamine-lesioned rats.
The induction of the early-gene c-fos after administration of the adenosine A2a receptor agonist CGS 21680, was studied in the striatum of normal rats or in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal neurons. CGS 21680 (2.25 mg/kg) induces c-fos expression in the 6-hydroxydopamine-lesioned striatum, while up to 40 mg/kg fails to induce c-fos in the intact striatum or in the striatum of normal rats. Blockade of muscarine receptors by scopolamine (5 mg/kg) partially prevents, and stimulation of dopamine D2 receptors by quinpirole (0.5 mg/kg) completely reverses, CGS 21680-induced c-fos expression in the 6-hydroxydopamine-lesioned striatum. In turn, CGS 21680 partially reverses c-fos expression induced by quinpirole in the lesioned globus pallidus. CGS 21680, in addition, dose-dependently reduces the turning behavior induced by quinpirole (0.5 mg/kg) in 6-hydroxydopamine-lesioned rats. The results suggest that CGS 21680 induces c-fos expression in the striatum through direct and indirect mechanisms related to the ability of A2a receptors to stimulate cyclic AMP formation or acetylcholine release which in turn would activate c-fos through muscarinic receptors.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D013563:Sympathectomy, Chemical
D000959:Antihypertensive Agents; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D018727:Muscarinic Antagonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019257:Quinpirole; D016627:Oxidopamine; D000241:Adenosine