Blockade of globus pallidus adenosine A(2A) receptors displays antiparkinsonian activity in 6-hydroxydopamine-lesioned rats treated with D(1) or D(2) dopamine receptor agonists.
We have recently demonstrated how antagonism of adenosine A(2A) receptors within the globus pallidus (GP) ipsilateral to dopaminergic denervation potentiates contralateral rotational behavior induced by the dopamine precursor L-DOPA in 6-hydroxydopamine-lesioned hemiparkinsonian rats. To further characterize the influence of pallidal A(2A) receptor blockade on the motor stimulant effects elicited by dopamine receptor activation, hemiparkinsonian rats were infused with the water-soluble A(2A) antagonist SCH BT2 in the GP, alone or in combination with systemic administration of either SKF 38393 or quinpirole, to stimulate dopamine D(1) or D(2) receptors, respectively. SCH BT2 alone (5 mug/1 mul) neither altered motor behavior nor produced postural asymmetry. In contrast, the contralateral rotations elicited by SKF 38393 (1.5 mg/kg) as well as quinpirole (0.05 mg/kg) were potentiated by the concomitant intrapallidal infusion of SCH BT2. The results of this study demonstrate that blockade of pallidal A(2A) receptors exerts a facilitatory influence on the motor effects produced by the selective stimulation of either D(1) or D(2) dopamine receptors in hemiparkinsonian rats and suggest an involvement of GP in the antiparkinsonian activity of A(2A) receptor antagonists.
Simola
Nicola
N
Department of Toxicology, University of Cagliari, 09124 Cagliari, Italy.
Fenu
Sandro
S
Baraldi
Pier G
PG
Tabrizi
Mojgan Aghazadeh
MA
Morelli
Micaela
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D006892:Hydroxydopamines; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control*; D011743:Pyrimidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013563:Sympathectomy, Chemical; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D006892:Hydroxydopamines; D018696:Neuroprotective Agents; D011743:Pyrimidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D014230:Triazoles; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine