Effects of adenosine A1, dopamine D1 and metabotropic glutamate 5 receptors-modulating agents on locomotion of the reserpinised rats.
The pathophysiology of Parkinson's disease and l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia are characterised by an imbalance between activity of the direct and indirect pathways regulated by dopamine D1 and D2 receptors, respectively. In this study, we investigated the effects of treatments combining adenosine A(1) and metabotropic glutamate 5 (mGlu5) receptors modulators on locomotion induced by dopamine D1 receptor activation in the reserpine-treated rats. Administration of the adenosine A(1) receptor agonist and mGlu5 receptor antagonist resulted in the significant reduction of dopamine D1 receptor agonist-induced locomotion. The combination of adenosine A(1) receptor agonist with mGlu5 receptor antagonist had no greater effect than these compounds alone. However, the adenosine A(1) receptor antagonist attenuated the inhibitory effect of mGlu5 receptor antagonist. The data suggest that the effect of mGlu5 receptor blockade on locomotion elicited by dopamine D1 receptor stimulation involves activation of adenosine A(1) receptors. This interaction can improve our understanding of pathophysiology of L-DOPA-induced dyskinesia.
The University of Manchester, School of Biological Sciences, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Naila
N
Ismayilova
Alan
A
Crossman
Alexei
A
Verkhratsky
Jonathan
J
Brotchie
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology*
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D015259:Dopamine Agents; D018683:Excitatory Amino Acid Agents; D043682:Receptor, Adenosine A1; D017447:Receptors, Dopamine D1; D018092:Kainic Acid Receptors; D012110:Reserpine