Striatal adenosine A(2A) receptor blockade increases extracellular dopamine release following l-DOPA administration in intact and dopamine-denervated rats

Gołembiowska, K; Dziubina, A

HERO ID

4933488

Reference Type

Journal Article

Year

2004

Language

English

PMID

15275831

HERO ID 4933488
In Press No
Year 2004
Title Striatal adenosine A(2A) receptor blockade increases extracellular dopamine release following l-DOPA administration in intact and dopamine-denervated rats
Authors Gołembiowska, K; Dziubina, A
Journal Neuropharmacology
Volume 47
Issue 3
Page Numbers 414-426
Abstract The influence of the selective adenosine A(2A) receptor antagonist ZM 241385 on exogenous l-DOPA-derived dopamine (DA) release in intact and dopamine-denervated rats was studied using an in vivo microdialysis in freely moving animals. Local infusion of l-DOPA (2.5 microM) produced a marked increase in striatal extracellular DA level in intact and malonate-lesioned rats. Intrastriatal perfusion of ZM 241385 (50-100 microM) had no effect on basal extracellular DA level, but enhanced dose-dependently the l-DOPA-induced DA release in intact and malonate-lesioned animals. A non-selective adenosine A(2A) receptor antagonist DMPX (100 microM), similarly to ZM 241385, accelerated conversion of l-DOPA in intact and malonate-denervated rats. This effect was not produced by the adenosine A(1) receptor antagonist, CPX (10-50 microM). However, ZM 241385 did not affect the l-DOPA-induced DA release in rats pretreated with reserpine (5 mg/kg i.p.) and alpha-methyl-p-tyrosine (AMPT, 300 mg/kg i.p.). Obtained results indicate that blockade of striatal adenosine A(2A) receptors increases the l-DOPA-derived DA release possibly by indirect mechanism exerted on DA terminals, an effect dependent on striatal tyrosine hydroxylase activity. Selective antagonists of adenosine A(2A) receptors may exert a beneficial effect at early stages of Parkinson's disease by enhancing the therapeutic efficacy of l-DOPA applied exogenously.
Doi 10.1016/j.neuropharm.2004.04.018
Pmid 15275831
Wosid WOS:000223235600012
Is Certified Translation No
Dupe Override No
Comments Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-3242690678&doi=10.1016%2fj.neuropharm.2004.04.018&partnerID=40&md5=ea7fdb0504a5a4f7ccbb7a26a653aaad
Is Public Yes
Language Text English
Keyword Index Medicus