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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概要
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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 × 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.
- 社団法人 日本実験動物学会の論文
著者
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TAKAGI Kenji
Department of Medical Technology, Nagoya University School of Health Sciences
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TAKAGI Kenzo
Department of Medical Technology, Nagoya University School of Health Sciences
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HASEGAWA Takaaki
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine
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KITAICHI Kiyoyuki
Department of Medical Technology, Nagoya University School of Health Sciences
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FUJIMOTO Yohei
Department of Medical Technology, Nagoya University School of Health Sciences
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ITO Yukiko
Department of Gastroenterology, Japanese Red Cross Medical Center
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Ito Yukiko
Department Of Gastroenterology Japanese Red Cross Medical Center
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Takagi Kenzo
Department Of Internal Medicine Nagoya University School Of Medicine
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Fujimoto Yohei
Department Of Aeronautics And Astronautics Kyushu University
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NAKAYAMA Hironao
Department of Medical Technology, Nagoya University School of Health Sciences
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Kitaichi Kiyoyuki
Department Of Cardiology Nagoya University Graduate School Of Medicine
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Hasegawa Takaaki
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Takagi Kenji
Department Of Cardiology Nagoya University Graduate School Of Medicine
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Nakayama Hironao
Department Of Biochemistry And Molecular Genetics Ehime University Graduate School Of Medicine
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ITO Yukiko
Department of Biopharmaceutics, Kyoto Pharmaceutical University
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HASEGAWA Takaaki
Department of Medical Technology, Nagoya University School of Health Sciences
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HASEGAWA Takaaki
Department of Bacteriology, Nagoya University School of Medicine
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