Effect of dopamine D2/D3 receptor antagonist sulpiride on amphetamine-induced changes in striatal extracellular dopamine
Effect of dopamine D2/D3 receptor antagonist sulpiride on amphetamine-induced changes in striatal extracellular dopamine
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DOI：
10.1016/s0014-2999(01)00936-0
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发表时间：
2001-04-27
影响因子：
5
通讯作者：
Randall, PK
中科院分区：
文献类型：
--
作者：
Jaworski, JN;Gonzales, RA;Randall, PK
苯丙胺增加细胞外多巴胺，并诱导大鼠的运动和刻板印象行为。本研究观察了多巴胺D2/D3受体拮抗剂舒必利(50 mg/kg S.C.)的作用。关于苯丙胺的多巴胺能反应(0.5，2.0.或8.0 mg/kg ip。)在雄性Spraogue-Dawley大鼠身上。采用体内微渗析和高效液相色谱-电化学检测相结合的方法对纹状体细胞外多巴胺进行监测。用非线性回归和残差F检验分析多巴胺浓度曲线。苯丙胺以剂量依赖的方式增强细胞外多巴胺。舒必利使0.5 mg/kg和2 mg/kg苯丙胺引起的多巴胺浓度升高的作用增强，其作用机制是降低细胞外间隙多巴胺浓度的下降速率(P<；0.05)。舒必利还可使多巴胺含量增加8 mg/kg苯丙胺。但这是通过影响达到的最大浓度来实现的(P<；0.05)，而不是通过影响起始或偏移率来实现的。我们的结论是，多巴胺D2/D3受体拮抗剂的主要作用是增强苯丙胺对细胞外纹状体多巴胺水平的影响，这可能有助于与苯丙胺配对时观察到的增强刻板印象效应。(C)2001年，爱思唯尔科学公司出版。
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. (C) 2001 Published by Elsevier Science B.V.