Methamphetamine influences on recognition memory: Comparison of escalating and single-day dosing regimens
Methamphetamine influences on recognition memory: Comparison of escalating and single-day dosing regimens
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DOI：
10.1038/sj.npp.1301510
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发表时间：
2008-05-01
影响因子：
7.6
通讯作者：
Marshall, John F.
中科院分区：
文献类型：
--
作者：
Belcher, Annabelle M.;Feinstein, Erin M.;Marshall, John F.
甲基苯丙胺（mAMPH）是一种成瘾性药物，会导致人类记忆和回忆障碍。接受破坏脑多巴胺和5-羟色胺末端的mAMPH过量给药方案的动物在物体识别（OR）任务中显示出损伤。早期的研究表明，在一天的mAMPH狂欢方案之前，增加mAMPH剂量的几天大大减弱了其在大鼠中的神经毒性。剂量递增（艾德）模式似乎模拟了人类药物摄入量递增的模式。目前的目的是测试是否艾德加狂饮mAMPH方案产生OR损害。除了它的翻译价值，这个实验有助于解决是否单胺能神经毒性占或mAMPH管理后看到的损害。为了进一步解决这个问题，一个单独的实验研究了在一天内用一系列mAMPH剂量处理的大鼠组中的OR损伤和单胺转运蛋白完整性。艾德mAMPH方案减弱了对随后mAMPH狂欢的急性高热反应，并防止了OR损伤和[I-125]RTI-55与纹状体、海马（HC）和嗅周皮质（pRh）中单胺转运体结合的减少，否则这些损伤和减少会在mAMPH狂欢后1周发生。单日mAMPH方案（4 x 1 mg/kg至4 x 4 mg/kg，皮下注射）剂量依赖性地产生急性高热，并且在mAMPH后1周，产生OR的剂量依赖性损害和单胺转运蛋白结合的减少。单天mAMPH处理大鼠的OR损伤与腹侧尾壳核、HC和pRh中单胺能转运蛋白的丢失相关。总的来说，这些发现表明mAMPH诱导的单胺能损伤和由此产生的OR缺陷之间的对应关系。
Methamphetamine (mAMPH) is an addictive drug that produces memory and recall impairments in humans. Animals subjected to a binge mAMPH dosing regimen that damages brain dopamine and serotonin terminals show impairments in an object recognition ( OR) task. Earlier research demonstrated that preceding a single-day mAMPH binge regimen with several days of increasing mAMPH doses greatly attenuates its neurotoxicity in rats. The escalating dose (ED) paradigm appears to mimic the human pattern of escalating drug intake. The current aim was to test whether an ED plus binge mAMPH regimen produces OR impairments. In addition to its translational value, this experiment helps address whether monoaminergic neurotoxicity accounts for OR impairments seen after mAMPH administration. To further address this issue, a separate experiment investigated both OR impairments and monoamine transporter integrity in groups of rats treated with a range of mAMPH doses during a single day. An ED mAMPH regimen attenuated the acute hyperthermic response to the subsequent mAMPH binge and prevented the OR impairments and reductions in [I-125]RTI-55 binding to monoamine transporters in striatum, hippocampus (HC), and perirhinal cortex (pRh) that otherwise occur 1 week after the mAMPH binge. Single-day mAMPH regimens (4 x 1 mg/kg to 4 x 4 mg/kg, s.c.) dose-dependently produced acute hyperthermia and, 1 week post-mAMPH, produced dose-dependent impairments in OR and reductions in monoamine transporter binding. The OR impairments of single-day mAMPH-treated rats correlated with monoaminergic transporter loss in ventral caudate-putamen, HC, and pRh. In aggregate, these findings suggest a correspondence between mAMPH-induced monoaminergic injury and the resulting OR deficits.