Neuropsychotoxicity of Abused Drugs : Involvement of Matrix Metalloproteinase-2 and -9 and Tissue Inhibitor of Matrix Metalloproteinase-2 in Methamphetamine-Induced Behavioral Sensitization and Reward in Rodents
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概要
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Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) function to remodel the pericellular environment. We have investigated the role of the MMP/TIMP system in methamphetamine (METH) dependence in rodents, in which the remodeling of neural circuits may be crucial. Repeated METH treatment induced behavioral sensitization, which was accompanied by an increase in MMP-2/-9/TIMP-2 activity in the brain. An antisense TIMP-2 oligonucleotide enhanced the sensitization, which was associated with a potentiation of the METH-induced release of dopamine in the nucleus accumbens (NAc). MMP-2/-9 inhibitors blocked the METH-induced behavioral sensitization and conditioned place preference (CPP), a measure of the rewarding effect of a drug, and reduced the METH-increased dopamine release in the NAc. In MMP-2– and MMP-9–deficient mice, METH-induced behavioral sensitization and CPP as well as dopamine release were attenuated. The MMP/TIMP system may be involved in METH-induced sensitization and reward by regulating extracellular dopamine levels.
- 社団法人 日本薬理学会の論文
- 2008-01-20
著者
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YAMADA Kiyofumi
Department of Neurosurgery, Graduate School of Medicine, Gifu University
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Nabeshima Toshitaka
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, J
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Yamada Kiyofumi
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Nabeshima Toshitaka
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Nabeshima Toshitaka
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Meijo University
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Mizoguchi Hiroyuki
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Mizoguchi Hiroyuki
Department Of Material Science And Ceramic Technology Shonan Institute Of Technology
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Yamada Kiyomi
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Yamada Kiyofumi
Dept. Of Neuropsychopharmacol. & Hosp. Pharm. Nagoya U. Sch. Of Med.
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Nabeshima Toshitaka
Dept. Of Neuropsychopharmacol. & Hosp. Pharm. Nagoya U. Sch. Of Med.
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Nabeshima Toshitaka
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Nabeshima Toshitaka
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Nabeshima Toshitaka
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Nabeshima Toshitaka
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Yamada Kiyofumi
Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med
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Nabeshima Toshitaka
Department Of Hospital Pharmacy School Of Medicine Nagoya University
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