Effect of dopamine D2/D3 receptor antagonist sulpiride on amphetamine-induced changes in striatal extracellular dopamine.

Abstract:

:Amphetamine increases extracellular dopamine and induces locomotor and stereotypical behaviors in rats. This study examined the effect of the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg s.c.) on the dopaminergic response to amphetamine (0.5, 2.0, or 8.0 mg/kg i.p.) in male Sprague-Dawley rats. Extracellular dopamine in the striatum was monitored using in vivo microdialysis and high performance liquid chromatography with electrochemical detection. Dopamine concentration curves were analyzed using non-linear regression and residual F-testing. Amphetamine enhanced extracellular dopamine in a dose-dependent manner. Sulpiride augmented the increase in dopamine induced by 0.5 and 2 mg/kg amphetamine by decreasing the rate of dopamine concentration fall off in the extracellular space (P<0.05). Sulpiride also potentiated the amount of dopamine increased by 8 mg/kg amphetamine, but did so by affecting the maximum concentration achieved (P<0.05), not the onset or offset rates. We conclude that the primary effect of a dopamine D2/D3 receptor antagonist is a potentiation of the effect of amphetamine on extracellular striatal dopamine levels, which may contribute to the enhanced stereotypic effects observed when paired with amphetamine.

journal_name

Eur J Pharmacol

authors

Jaworski JN,Gonzales RA,Randall PK

doi

10.1016/s0014-2999(01)00936-0

keywords:

subject

Has Abstract

pub_date

2001-04-27 00:00:00

pages

201-6

issue

3

eissn

0014-2999

issn

1879-0712

pii

S0014299901009360

journal_volume

418

pub_type

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