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Effect of tolcapone, a catechol-O-methyltransferase inhibitor, on striatal dopaminergic transmission during blockade of dopamine uptake.

Abstract：

:To examine the mechanisms of tolcapone in the central nervous system (CNS), we analyzed alterations in parameters of striatal dopamine transmission induced by this drug (30 mg/kg) co-administered with the selective dopamine uptake inhibitor, GBR 12909 (10 mg/kg). Using microdialysis in freely moving rats, it was determined that combined administration of tolcapone with GBR 12909 resulted in a further increase of dopamine levels over that obtained without the catechol-O-methyltransferase inhibitor, while tolcapone alone failed to change dopamine levels. Fast-scan cyclic voltammetric monitoring of electrically evoked dopamine did not show any changes in dopamine release after the combination of the drugs, but there was a pronounced decrease in the rate of dopamine clearance after GBR 12909 alone and when co-administered with tolcapone. These data indicate that in rat striatum, a tolcapone-induced increase in extracellular dopamine is not observed because of the presence of uptake. These results also support the hypothesis that under normal conditions, uptake, rather than metabolism, control extracellular levels of dopamine.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Budygin EA,Gainetdinov RR,Kilpatrick MR,Rayevsky KS,Männistö PT,Wightman RM

doi

10.1016/s0014-2999(99)00084-9

keywords:

subject

Has Abstract

pub_date

1999-04-09 00:00:00

pages

125-31

issue

2

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(99)00084-9

journal_volume

370

pub_type

杂志文章

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