Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A(2A) receptors in the caudate-putamen of rats.
The present study sought to determine, in more detail, the effects of an unselective and a selective adenosine A(2A) receptor blockade on catalepsy induced by a blockade of dopamine D1 or D2 receptors in rats. The results demonstrated that systemic administration of the unselective A1/A2 receptor antagonist, theophylline and the selective A(2A) receptor antagonist, CSC potently reversed catalepsy induced by a systemic D2 receptor blockade with raclopride or by a bilateral blockade of D2 receptors in the caudate-putamen (CPu) with S(-)sulpiride. Likewise, systemic administration of theophylline and CSC reversed catalepsy induced by a systemic D1 receptor blockade with SCH23390; theophylline also counteracted catalepsy after an intra-CPu D1 receptor blockade with SCH23390. Intracerebral co-microinfusions of the selective A(2A) receptor antagonist, MSX-3 together with a D1 (SCH23390) or D2 receptor [S(-) sulpiride] antagonist revealed that catalepsy due to intra-CPu D1 or D2 receptor blockade can be potently reversed by an intra-CPu A2A receptor blockade. In conclusion, our results with systemic and intra-CPu drug administration demonstrate that D1 and D2 receptor-mediated catalepsy can both be reversed by a concomitant blockade of A(2A) receptors. Our results implicate that the CPu is a critical neural substrate for antagonistic interactions of a D1/D2 receptor blockade and an A(2A) receptor blockade in control of motor activity. The present results provide further support for the view that A(2A) receptor antagonists may be potential therapeutics for the treatment of Parkinson's disease.
Hauber
W
W
Department of Animal Physiology, Institute of Biology, University of Stuttgart, D-70550 Stuttgart, Germany. wolfgang.hauber@po.uni-stuttgart.de
Neuscheler
P
P
Nagel
J
J
Müller
C E
CE
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; C113602:MSX 3 compound; D010726:Phosphodiesterase Inhibitors; D011355:Prodrugs; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D014970:Xanthines; D013469:Sulpiride; D013806:Theophylline; D000241:Adenosine