Friedman S D, Castañeda E, Hodge G K
University of New Mexico, Department of Psychology, Albuquerque, USA.
Pharmacol Biochem Behav. 1998 Sep;61(1):35-44. doi: 10.1016/s0091-3057(98)00066-5.
Squads of rats were assayed at three intervals following MA-induced neurotoxicity to investigate the persistence of monoamine deficits, the potential for monoamine recovery, and spatial task abilities. At 48, 139, and 237 days postinjection, MA animals showed significant monoamine depletions compared with controls. Investigating percent depletions (MA/control) across time showed monoamine recovery in some structures. Initially, 5-HT within medial prefrontal cortex (MPFC), caudate (CdN), and hippocampus (HPC) was reduced to 30% of control levels. By 237 days, MPFC and CdN levels were elevated to 70%. Similarly, initial CdN DA reductions (30% of control levels) showed recovery to 80% by 237 days. These findings support neurochemical recovery following MA neurotoxicity. However, the persistent depression of HPC 5-HT suggests that not all structures recover equally. The HPC did show elevated turnover (metabolite/neurotransmitter) over time, suggesting a unique compensatory response. MA treatment also produced an impairment in the Morris water-maze place task at 65 days postinjection. No impairments were observed in water-maze moving platform or place task at 79 and 165 days postinjection, respectively, or in T-maze alternation. The possibility that partial recovery in tissue monamine levels underlies the sparing of function and behavioral improvement is discussed.
在甲基苯丙胺（MA）诱导的神经毒性后的三个时间点对大鼠进行检测，以研究单胺缺乏的持续性、单胺恢复的可能性以及空间任务能力。在注射后48天、139天和237天，与对照组相比，MA处理的动物出现了明显的单胺耗竭。对不同时间点的耗竭百分比（MA/对照组）进行研究发现，某些脑区的单胺有所恢复。最初，内侧前额叶皮质（MPFC）、尾状核（CdN）和海马体（HPC）中的5-羟色胺（5-HT）降至对照组水平的30%。到237天时，MPFC和CdN中的水平升高到70%。同样，最初CdN中的多巴胺（DA）减少（降至对照组水平的30%），到237天时恢复到80%。这些发现支持了MA神经毒性后的神经化学恢复。然而，HPC中5-HT的持续降低表明并非所有脑区都能同等程度地恢复。随着时间推移，HPC确实显示出周转率（代谢物/神经递质）升高，表明存在独特的代偿反应。MA处理在注射后65天还导致了Morris水迷宫定位任务受损。在注射后79天和165天，分别在水迷宫移动平台或定位任务中以及在T迷宫交替任务中未观察到损伤。文中讨论了组织中单胺水平的部分恢复是功能保留和行为改善基础的可能性。
