Involvement of globus pallidus in the antiparkinsonian effects of adenosine A(2A) receptor antagonists.
An involvement of globus pallidus (GP) in the antiparkinsonian effects of A(2A) receptor antagonists has been proposed on the basis of the selective localization of A(2A) receptors on the striatopallidal pathway. In order to investigate this possibility, the present study evaluated rotational behavior in unilaterally 6-hydroxydopamine-lesioned rats following infusion of the water-soluble A(2A) receptor antagonist SCH BT2 into GP. SCH BT2 (5 microg/1 microl) altered neither motor behavior nor produced postural asymmetry by itself. However, when infused concomitantly with a parenteral subthreshold dose of l-DOPA (3 mg/kg i.p.) capable of inducing modest contralateral rotational behavior (34.7 +/- 20.7/1 h), SCH BT2 significantly potentiated the number of contraversive rotations (167.4 +/- 16.3/1 h). These results suggest that A(2A) receptors located in the globus pallidus may be involved in the antiparkinsonian effects of A(2A) antagonists.
Simola
Nicola
N
Department of Toxicology and Centre of Excellence for Neurobiology of Dependence, University of Cagliari, 09124 Cagliari, Italy.
Fenu
Sandro
S
Baraldi
Pier G
PG
Tabrizi
Mojgan Aghazadeh
MA
Morelli
Micaela
M
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D007839:Functional Laterality / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology*; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
C492656:2-furan-2-yl-7-3-(4-(4-(4-methylpiperazine-1-sulfonyl)phenylethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo-(1,5-c)pyrimdin-5-ylamine); D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D010879:Piperazines; D011743:Pyrimidines; D007980:Levodopa; D016627:Oxidopamine