Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis
Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis
复制标题
体内透析揭示苯环己哌啶和甲基苯丙胺对大鼠额叶皮层和纹状体多巴胺代谢的不同影响
作者：
K. Nishijima;A. Kashiwa;A. Hashimoto;H. Iwama;A. Umino;T. Nishikawa
我们研究了拟精神分裂症药物，包括苯环利定（PCP）和甲基苯丙胺（MAP）对皮质和纹状体多巴胺（DA）代谢的影响，在大鼠体内透析技术。急性全身注射五氯苯酚（2.5-10 mg/kg，腹膜内（i. p.））内侧额叶皮质透析液中DA、3，4-二羟基-苯乙酸和高香草酸的浓度以剂量依赖性方式显著增加。然而，五氯苯酚（2.5-10毫克/千克，i. p.）导致细胞外DA释放的增加低得多，纹状体中透析液DOPAC水平显著降低。此外，通过微透析管将河豚毒素（TTX，10 - 5 M）连续输注到前额或纹状体区域完全阻断PCP（10 mg/kg，i. p.）以改变DA及其代谢物在相应区域中的细胞外释放。相比之下，MAP（4.8mg/kg，i. p.）引起DA水平的显著和河豚毒素抗性增加，额叶皮质和纹状体的细胞外间隙中DOPAC含量显著损失。目前的结果清楚地表明PCP对皮质和纹状体DA传递的不同影响，表明PCP可能通过增加投射到皮质区的DA神经元中的冲动流来促进内侧额叶皮质中的DA释放，而PCP诱导的纹状体中细胞外DA的升高可能主要是由纹状体DA神经元的基础活动释放的DA的再摄取抑制引起的。PCP诱导的DA释放的区域差异可能是由于NMDA（N-甲基-D-天冬氨酸）受体阻断和药物对DA再摄取的抑制作用。MAP诱导的脑DA代谢变化的一致性和TTX抗性性质可能是由于MAP对DA神经末梢的直接作用。© 1996 Wiley利斯公司
We have examined the effects of schizophrenomimetic drugs including phencyclidine (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism using an in vivo dialysis technique in the rat. An acute systemic injection of PCP (2.5–10 mg/kg, intraperitoneally (i.p.)) dramatically increased concentrations of DA, 3,4‐dihydroxy‐phenylacetic acid, and homovanillic acid in the dialysates from the medial frontal cortex in a dose‐dependent fashion. However, PCP (2.5–10 mg/kg, i.p.) caused a much lower augmentation of extracellular DA release, with a significant decrease in dialysate DOPAC levels in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10−5 M) into the prefrontal or striatal region through the microdialysis tube completely blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg, i.p.) elicited a marked and tetrodotoxin‐resistant increase in DA levels with a significant loss of DOPAC contents in the extracellular space of both the frontal cortex and the striatum. The present results clearly demonstrate the differential effects of PCP on cortical and striatal DA transmission, suggesting that PCP may facilitate DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area, whereas PCP‐induced elevation of extracellular DA in the striatum may be caused mainly by reuptake inhibition of DA liberated by basal activity of the striatal DA neurons. The regional variation in PCP‐induced DA release would be due to the combination of NMDA (N‐methyl‐D‐aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform and TTX‐resistant nature of MAP‐induced changes in brain DA metabolism may result from the direct actions of MAP at DA nerve terminals. © 1996 Wiley‐Liss, Inc.
影响因子：
5
作者：
Arthur S. Freeman;Benjamin S. Bunney
通讯作者：
Arthur S. Freeman;Benjamin S. Bunney
影响因子：
5
作者：
DEUTCH, AY;TAM, SY;ROTH, RH
通讯作者：
ROTH, RH
安非他明是否会优先增加自由活动大鼠中脑边缘系统中多巴胺的细胞外浓度？
DOI：
--
发表时间：
1990
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Robinson,TE;Camp,DM
通讯作者：
Camp,DM