The pharmacokinetic properties of methamphetamine in rats with previous repeated exposure to methamphetamine: The differences between Long-Evans and Wistar rats
The pharmacokinetic properties of methamphetamine in rats with previous repeated exposure to methamphetamine: The differences between Long-Evans and Wistar rats
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DOI：
10.1538/expanim.56.119
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发表时间：
2007-04-01
影响因子：
2.4
通讯作者：
Hasegawa, Takaaki
中科院分区：
文献类型：
--
作者：
Fujimoto, Yohei;Kitaichi, Kiyoyuki;Hasegawa, Takaaki
反复使用甲基苯丙胺（冰毒）会导致人类和实验动物的长期行为改变，即所谓的行为致敏（BS）。然而，没有关于反复冰毒治疗是否能在应激敏感的Long-Evans （LE）大鼠中建立BS的报道。因此，我们研究了反复给药（5 mg/kg x 5天）对LE大鼠BS建立的影响。以Wistar （WIS）大鼠为对照。在LE大鼠中，反复的冰毒治疗没有引起BS，尽管它确实增强了冰毒诱导的WIS大鼠的过度运动。如前所述，重复冰毒治疗的WIS大鼠脑透析液中冰毒的含量和血浆中浓度-时间曲线下面积与脑透析液中冰毒的比值升高，而重复冰毒治疗的LE大鼠脑透析液中冰毒的含量没有升高。甲基苯丙胺增加血浆皮质酮（CORT）在两个菌株。然而，LE大鼠经反复甲基安非他明后，CORT的增加强度低于WIS大鼠。反复冰毒处理可降低WIS大鼠脑内甲基甲醚转座转运体和cort敏感转运体有机阳离子转运体3 （OCT3）的表达。然而，两种菌株经反复甲基安非他明处理后，OCT3的衰减强度相似。综上所述，这些结果表明，LE大鼠缺乏BS的建立可能是由于反复给药后甲基安非他明未改变脑渗透，并且对甲基安非他明的不同CORT反应是一个重要的品系差异。
Repeated treatment with methamphetamine (METH) causes long-term behavioral changes, so-called behavioral sensitization (BS), in humans as well as experimental animals. However, there are no reports as to whether repeated METH treatment can establish BS in stress-sensitive Long-Evans (LE) rats. Thus, we investigated the effect of repeated METH treatment (5 mg/kg x 5 days) on the establishment of BS in LE rats. Wistar (WIS) rats were used as a reference. In LE rats, repeated METH treatment failed to cause BS although it did enhance METH-induced hyperlocomotion in WIS rats. The levels of METH in brain dialysate and the ratio of the area under the concentration-time curve area in plasma to that in brain dialysate was increased in repeated METH-treated WIS rats as reported previously, but not in repeated METH-treated LE rats. METH increases plasma corticosterone (CORT) in both strains. However, the intensity of increment of CORT by repeated METH was lower in LE rats than that in WIS rats. Repeated METH treatment decreased the expression of METH-transposable and CORT-sensitive transporter, organic cation transporter 3 (OCT3), in the brain of WIS rats. However, the intensity of the decrement of OCT3 with repeated METH treatment was similar between both strains. Taken together, these results suggest that the lack of establishment of BS in LE rats might have been caused by the unchanged brain penetration of METH after repeated METH administration, and that the differential CORT response to METH is an important strain difference.