EFFECTS OF REPEATED ADMINISTRATION OF A HIGH-DOSE OF METHAMPHETAMINE ON DOPAMINE AND GLUTAMATE RELEASE IN RAT STRIATUM AND NUCLEUS-ACCUMBENS
EFFECTS OF REPEATED ADMINISTRATION OF A HIGH-DOSE OF METHAMPHETAMINE ON DOPAMINE AND GLUTAMATE RELEASE IN RAT STRIATUM AND NUCLEUS-ACCUMBENS
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DOI：
10.1016/0006-8993(94)90033-7
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发表时间：
1994-04-18
期刊：
影响因子：
2.9
通讯作者：
KOYAMA, T
中科院分区：
文献类型：
--
作者：
ABEKAWA, T;OHMORI, T;KOYAMA, T
我们检查了高剂量甲基苯丙胺（MA）（4.02 mg游离碱/kg，s.c.，以2小时间隔，4次注射）对细胞外单胺类如多巴胺（DA）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）和5-羟基吲哚乙酸（5-HIAA）以及谷氨酸和其它几种氨基酸浓度的影响。微透析后5天，测量组织中单胺的浓度。中毒剂量的MA使ST和NA细胞外DA浓度显著升高，DOPAC、HVA和5-HIAA浓度显著降低。DA释放增加的幅度在ST和NA之间没有差异。谷氨酸的细胞外浓度显示ST逐渐增加，但不是在NA，而其他氨基酸显示ST和NA没有变化。5-HT和5-HIAA的组织浓度在ST和NA中均下降至对照值的43-58%，而DA、DOPAC和HVA的组织浓度在ST中下降43-54%，但在NA中无变化。这些数据表明，DA释放的显着增加是没有直接相关的MA诱导的多巴胺能神经毒性。仅在ST中发现的谷氨酸释放的增加可能与ST中的多巴胺能损伤有关。然而，谷氨酸释放的增强似乎不是MA诱导的多巴胺能神经毒性所必需的。
We examined effects of a high dose of methamphetamine (MA) (4.02 mg free base/kg, s.c., at 2-h intervals, 4 injections) on extracellular concentrations of monoamines such as dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) and those of glutamate and other several amino acids in rat striatum (ST) and nucleus accumbens (NA) using in vivo microdialysis. Five days after the microdialysis, tissue concentrations of monoamines were measured. The toxic dose of MA markedly increased extracellular concentrations of DA, and decreased those of DOPAC, HVA and 5-HIAA in both ST and NA. Magnitude of the increase in DA release was not different between ST and NA. Extracellular concentrations of glutamate showed a gradual increase in ST, but not in NA, while other amino acids showed no changes in both ST and NA. Tissue concentrations of serotonin (5-HT) and 5-HIAA were decreased to 43-58% of control values in both ST and NA, whereas those of DA, DOPAC and HVA showed 43-54% decreased in ST but no changes in NA. These data suggest that the marked increase in DA release is not directly related to the MA-induced dopaminergic neurotoxicity. The increase in glutamate release found only in ST may be related to the dopaminergic damage in ST. However, enhancement in glutamate release did not appear to be essential for the MA-induced serotonergic neurotoxicity.