Cass W A, Manning M W
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
J Neurosci. 1999 Sep 1;19(17):7653-60. doi: 10.1523/JNEUROSCI.19-17-07653.1999.
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.
对动物反复给予甲基苯丙胺（METH）可导致纹状体多巴胺（DA）含量长期降低。此外，给予神经毒性剂量的METH后1周，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会随时间恢复尚未明确。在本研究中，我们使用体内电化学和微透析技术，在给药后的几个时间点检测METH处理大鼠纹状体中DA的诱发溢出，以确定DA溢出是否会自发恢复。雄性Fischer-344大鼠在一天内每隔2小时接受4次METH（5mg/kg，皮下注射）或生理盐水注射。在给药后1周、1个月、6个月和12个月，分别对麻醉大鼠进行体内电化学实验，对清醒大鼠进行体内微透析研究。给药后1周，METH处理动物的纹状体中，钾离子和苯丙胺诱发的DA溢出以及DA的清除率均显著降低。DA及其代谢产物的基础细胞外水平也降低。到1个月时，诱发溢出已部分恢复。到6个月时，METH处理大鼠的DA诱发溢出似乎已恢复正常。然而，纹状体DA的全组织水平仍显著降低。到12个月时，所有参数均恢复到对照值。这些结果表明，给药后12个月，METH处理大鼠纹状体中突触前多巴胺能功能可恢复到正常水平。
