Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine
Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine
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DOI：
10.1523/jneurosci.19-17-07653.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Manning, MW
中科院分区：
文献类型：
--
作者：
Cass, WA;Manning, MW
反复给动物服用甲基苯丙胺会导致纹状体多巴胺(DA)含量的长期下降。此外，神经毒性剂量的冰毒1周后，大鼠纹状体DA的诱发溢出减少。然而，DA释放的这些功能变化是永久性的，还是随着时间的推移而趋于恢复，目前还没有确定。在本研究中，我们用体内电化学和微透析的方法检测了冰毒治疗后不同时间点纹状体DA的诱发溢出，以确定DA的溢出是否会自发恢复。雄性Fischer-344大鼠皮下注射冰毒5 mg/kg。或生理盐水，每天四次，间隔2小时。分别于给药后1周、1个月、6个月和12个月进行麻醉大鼠体内电化学实验和清醒大鼠体内微透析实验。用药后1周，冰毒处理组大鼠纹状体中钾离子和苯丙胺引起的DA溢出和DA清除均显著减少。基础细胞外多巴胺及其代谢物水平也降低。诱发的溢流在1个月时部分恢复。到6个月时，冰毒处理组大鼠的DA诱发溢出似乎是正常的。然而，纹状体DA的整个组织水平仍显著下降。所有参数在12个月时均恢复到对照水平。这些结果表明，冰毒治疗12个月后，纹状体中的突触前多巴胺能功能可以恢复到正常水平。
Repeated administration of methamphetamine (METH) to animals can result in long-lasting decreases in striatal dopamine (DA) content. In addition, the evoked overflow of striatal DA is reduced in rats 1 week after neurotoxic doses of METH. However, whether these functional changes in DA release are permanent or tend to recover over time has not been established. In the present study we used in vivo electrochemistry and microdialysis to examine evoked overflow of DA in the striatum of METH-treated rats at several time points after treatment to determine if DA overflow would spontaneously recover. Male Fischer-344 rats were administered METH (5 mg/kg, s.c.) or saline four times in one day at 2 hr intervals. In vivo electrochemistry experiments in anesthetized rats, and in vivo microdialysis studies in awake rats, were carried out 1 week, 1 month, 6 months, and 12 months after treatment. At 1 week after treatment there were significant decreases in potassium- and amphetamine-evoked overflow of DA, and in clearance of DA, in the striatum of the METH-treated animals. Basal extracellular levels of DA and its metabolites were also decreased. Evoked overflow had partially recovered by 1 month. By 6 months evoked overflow of DA appeared to be normal in the METH-treated rats. However, whole tissue levels of striatal DA were still significantly decreased. All parameters were back to control values by 12 months. These results suggest that presynaptic dopaminergic functioning can recover to normal levels in the striatum of METH-treated rats by 12 months after treatment.