Synergistic interaction between an adenosine antagonist and a D1 dopamine agonist on rotational behavior and striatal c-Fos induction in 6-hydroxydopamine-lesioned rats.
The interaction between adenosine and D1 dopamine systems in regulating motor behavior and striatal c-Fos expression was examined in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. These results were compared to the synergistic interaction between D1 and D2 dopamine systems in 6-OHDA rats. Coadministration of the adenosine antagonist 3,7-dimethyl-1-propargylxanthine (DMPX: 10 mg/kg) and the D1 dopamine agonist SKF38393 (0.5 mg/kg) to 6-OHDA-lesioned rats produced significant contralateral rotation and c-Fos expression in the ipsilateral striatum compared to 6-OHDA rats treated with either drug alone. However, the regional pattern of striatal c-Fos activation following treatment of 6-OHDA rats with SKF38393 and DMPX was different from the dorsolateral pattern of striatal c-Fos induction observed after coadministration of D1 and D2 dopamine agonists (SKF38393: 0.5 mg/kg + quinpirole: 0.05 mg/kg). These data are consistent with a functional interaction between D1 dopamine and adenosine systems in the striatum, but suggest that activation of different subsets of striatal neurons underlie the behavioral synergy observed following combined adenosine antagonist-D1 dopamine agonist and combined D1 dopamine agonist-D2 dopamine agonist treatment.
Pollack
A E
AE
Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, USA.
Fink
J S
JS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D007839:Functional Laterality / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins; D016627:Oxidopamine; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012399:Rotation; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology
D018491:Dopamine Agonists; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D058915:Purinergic P1 Receptor Antagonists; D017447:Receptors, Dopamine D1; C057837:3,7-dimethyl-1-propargylxanthine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D013805:Theobromine