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

Amphetamine increases extracellular dopamine and induces locomotor and ster eotypical behaviors in rats. This study examined the effect of the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg s.c.) on the dopaminergic re sponse 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 mi crodialysis and high performance liquid chromatography with electrochemical detection. Dopamine concentration curves were analyzed using non-linear re gression and residual F-testing. Amphetamine enhanced extracellular dopamin e 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 c oncentration fall off in the extracellular space (P < 0.05). Sulpiride also potentiated the amount of dopamine increased by 8 mg/kg amphetamine. but d id so by affecting the maximum concentration achieved (P < 0.05), not the o nset 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 ex tracellular striatal dopamine levels, which may contribute to the enhanced stereotypic effects observed when paired with amphetamine. (C) 2001 Publish ed by Elsevier Science B.V.