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吡贝地尔和溴隐亭对多巴胺代谢产物的区域和动力学差异效应:自由活动大鼠的脑微透析研究

Differential regional and kinetics effects of piribedil and bromocriptine on dopamine metabolites: a brain microdialysis study in freely moving rats.

作者信息

Pagliari R, Peyrin L, Crambes O

机构信息

Laboratoire de Physiologie, Faculté de Médecine, Lyon.

出版信息

J Neural Transm Gen Sect. 1995;101(1-3):13-26. doi: 10.1007/BF01271542.

Abstract

Brain microdialysis coupled to HPLC was applied to freely moving rats to investigate the regional kinetics of piribedil and bromocriptine on the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatum, nucleus accumbens, and frontal cortex. Both D2 agonists (20 mg/kg i.p.) decreased DOPAC and HVA in the three brain regions. The responsiveness of frontal cortex to both compounds was greater than those previously reported with other dopaminergic drugs. Regional and temporal differences were observed under piribedil: DOPAC and HVA levels decreased more in the nucleus accumbens than in striatum or frontal cortex but increased over basal values from the 5th hour in the frontal cortex suggesting a late stimulatory effect of piribedil on dopamine synthesis in this area. Such regional effects differentiate piribedil from most other D2 agonists and could explain some behavioural and therapeutic actions possibly related to involvement of nucleus accumbens or/and frontal cortex.

摘要

将脑微透析与高效液相色谱联用,应用于自由活动的大鼠,以研究吡贝地尔和溴隐亭对纹状体、伏隔核和额叶皮质细胞外3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)水平的区域动力学。两种D2激动剂(腹腔注射20mg/kg)均降低了三个脑区的DOPAC和HVA。额叶皮质对这两种化合物的反应性高于先前报道的其他多巴胺能药物。在吡贝地尔作用下观察到区域和时间差异:伏隔核中DOPAC和HVA水平的下降幅度大于纹状体或额叶皮质,但额叶皮质从第5小时起高于基础值,表明吡贝地尔对该区域多巴胺合成有后期刺激作用。这种区域效应使吡贝地尔与大多数其他D2激动剂不同,并且可以解释一些可能与伏隔核或/和额叶皮质参与有关的行为和治疗作用。

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