Adenosine antagonists potentiate D2 dopamine-dependent activation of Fos in the striatopallidal pathway.
Adenosine antagonists potentiate dopamine-mediated behaviours. A2a adenosine and D2 dopamine receptors are abundantly co-expressed within the striatopallidal subset of striatal neurons, suggesting that this is the site of interaction between A2a and D2 receptors. We show that the D2-dependent induction of the immediate early gene c-Fos occurs in striatopallidal neurons 3 h following injection of reserpine (10 mg/kg). We used this paradigm to test whether adenosine antagonists modulate D2-dependent activation of striatopallidal neurons. The non-selective A1-A2 adenosine antagonists theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) potentiated the effect of a submaximal dose of the D2 dopamine agonist quinpirole (0.05 mg/kg) to prevent the induction of striatal c-Fos following reserpine. Co-administration of the A2a receptor antagonist 8-(3-chlorostyryl) caffeine (5 mg/kg) with quinpirole (0.05 mg/kg) also attenuated striatal c-Fos induction following reserpine to a greater extent than 0.05 mg/kg quinpirole alone. When administered prior to reserpine, theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) partially attenuate the induction of striatal c-fos. These results demonstrate that systemic administration of adenosine antagonists enhance D2 dopamine receptor-dependent regulation of c-Fos in the striatopallidal pathway. These results support a functional interaction between A2a adenosine and D2 dopamine receptors in striatopallidal neurons.
Pollack
A E
AE
Department of Neurology, Massachusetts General Hospital, Boston 02114, USA.
Fink
J S
JS
D000241:Adenosine / Q000037:antagonists & inhibitors*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D016762:Genes, fos / Q000187:drug effects*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012110:Reserpine / Q000494:pharmacology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D018491:Dopamine Agonists; D004873:Ergolines; D010726:Phosphodiesterase Inhibitors; D017448:Receptors, Dopamine D2; C081320:8-(3-chlorostyryl)caffeine; D019257:Quinpirole; D002110:Caffeine; C057837:3,7-dimethyl-1-propargylxanthine; D012110:Reserpine; D013806:Theophylline; D000241:Adenosine; D013805:Theobromine