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苯丙胺、可卡因及高钾去极化对自发性高血压大鼠伏隔核壳外多巴胺的影响。一项体内微透析研究。

Effect of amphetamine, cocaine and depolarization by high potassium on extracellular dopamine in the nucleus accumbens shell of SHR rats. An in vivo microdyalisis study.

作者信息

Carboni Ezio, Silvagni Alessandra, Valentini Valentina, Di Chiara Gaetano

机构信息

Department of Toxicology, Centro di Eccellenza sulla Neurobiologia delle Dipendenze, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.

出版信息

Neurosci Biobehav Rev. 2003 Nov;27(7):653-9. doi: 10.1016/j.neubiorev.2003.08.008.

Abstract

Spontaneously hypertensive rats (SHR) exhibit behavioural abnormalities (hyperactivity and hyper reactivity to stress) that resemble the behavioural abnormalities of human attention-deficit with hyperactivity disorder (ADHD). Because dopamine has been implicated in ADHD we studied by in vivo microdialysis the dopamine output in the nucleus accumbens (NAc) shell of 6 week-old (pre-hypertensive stage) SHR rats and in their normotensive age matched Wistar Kyoto controls (WKY). We observed that SHR rats had significant higher basal dialysate dopamine concentrations (about 20%) than WKY. Systemic administration of amphetamine (0.25 and 0.5 mg/kg s.c.), and methylphenidate (1 and 2 mg/kg i.p.) produced an higher increase in dialysate dopamine in the NAc shell of SHR rats as compared with WKY rats, although only after the administration of the lowest dose of amphetamine and methylphenidate this difference was found to be significant. In contrast when the microdialysis fiber was perfused by 30 or 60 mM K(+), a lower increase of dialysate dopamine was observed in SHR rats as compared with WKY rats. These apparently contradictory results can be explained by postulating that SHR rats have a higher tone of NAc shell dopamine transmission and synthesis associated with a lower storage capacity of vesicles in dopamine terminals of the same area.

摘要

自发性高血压大鼠(SHR)表现出行为异常(多动和对应激的高反应性),类似于人类注意力缺陷多动障碍(ADHD)的行为异常。由于多巴胺与ADHD有关,我们通过体内微透析研究了6周龄(高血压前期)SHR大鼠伏隔核(NAc)壳中的多巴胺输出,并与其年龄匹配的正常血压Wistar Kyoto对照大鼠(WKY)进行了比较。我们观察到,SHR大鼠的基础透析液多巴胺浓度比WKY大鼠显著高约20%。与WKY大鼠相比,对SHR大鼠全身注射苯丙胺(0.25和0.5mg/kg,皮下注射)和哌甲酯(1和2mg/kg,腹腔注射)后,NAc壳中的透析液多巴胺增加更高,不过只有在注射最低剂量的苯丙胺和哌甲酯后,这种差异才具有统计学意义。相反,当微透析纤维用30或60mM K(+)灌注时,与WKY大鼠相比,SHR大鼠的透析液多巴胺增加较低。这些明显矛盾的结果可以通过假设SHR大鼠NAc壳多巴胺传递和合成的张力较高,而同一区域多巴胺终末中囊泡的储存能力较低来解释。

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