Clark Robert E, Kuczenski Ronald, Segal David S
Veterans Affairs Medical Center, San Diego, California, USA.
Synapse. 2007 Jul;61(7):515-22. doi: 10.1002/syn.20397.
Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.
据报道，以急性高剂量“狂欢”模式接触甲基苯丙胺（METH）的大鼠在新颖物体识别（NOR）任务中表现出持续的缺陷，这可能表明人类甲基苯丙胺滥用者存在潜在风险。然而，大多数高剂量甲基苯丙胺滥用者最初使用较低剂量，然后逐渐增加剂量，最终才会每天多次用药。为了模拟这种甲基苯丙胺接触模式，我们在14天的间隔内给大鼠逐渐增加甲基苯丙胺的剂量，然后连续11天对它们进行每日甲基苯丙胺“狂欢”治疗。这种治疗导致纹状体多巴胺（DA）水平持续下降约20%。然后，我们在各种条件下对它们进行NOR任务测试。在任何测试条件下，我们都未检测到它们在NOR任务中的表现存在缺陷。这些结果表明，与急性甲基苯丙胺“狂欢”相关的纹状体多巴胺减少之外或与之相关的其他机制是NOR任务缺陷的原因，并且长期递增剂量甲基苯丙胺预处理导致的神经适应性变化可减轻这些机制的影响。
