SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum.
In the striatum, dopamine D(2) receptors are co-localized with adenosine A(2A) receptors on the GABAergic neurons of the striopallidal pathway. Moreover, blockade of A(2A) receptors has been previously shown to suppress parkinsonian-like symptoms (catalepsy, akinesia, muscle rigidity) in rodent and primate models of Parkinson's disease (PD). Since it is believed that main motor symptoms of PD are due to the overactivity of the GABAergic striopallidal pathway, the aim of the present study was to find out whether SCH 58261, a selective antagonist of the adenosine A(2A) receptors, is capable of counteracting both the catalepsy and the enhancement of proenkephalin (PENK) mRNA expression in the rat striatum, induced by haloperidol administered at 1.5 mg/kg s.c. 3 times, every 3 h. Systemic administration of SCH 58261 (5 mg/kg i.p., 3 times, every 3 h, 10 min before haloperidol), partially decreased the haloperidol-induced catalepsy and the increase in the PENK mRNA expression in both dorsolateral and ventrolateral parts of the striatum at all three examined levels. No such changes were seen in the medial striatum and in the nucleus accumbens. Moreover, SCH 58261 given alone did not influence the level of PENK mRNA in any examined part of the striatum. The present results suggest that similarly to other A(2A) receptor antagonists, SCH 58261 normalizes activity of the striopallidal pathway, enhanced by blockade of dopamine D(2) receptors with haloperidol, which may result in recovery of motor functions.
Wardas
Jadwiga
J
Department of NeuroPsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 Kraków, Poland. wardas@if-pan.krakow.pl
Pietraszek
Małgorzata
M
Dziedzicka-Wasylewska
Marta
M
D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D043705:Receptor, Adenosine A2A; 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; D018492:Dopamine Antagonists; D004745:Enkephalins; D011498:Protein Precursors; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C029992:proenkephalin; D006220:Haloperidol