Drug Dependence, Synaptic Plasticity, and Tissue Plasminogen Activator
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概要
- 論文の詳細を見る
The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the system is involved in drug dependence. A DNA microarray screening revealed that the expression levels of tissue plasminogen activator (tPA) mRNA in the nucleus accumbens of morphine- or methamphetamine-dependent rats were significantly increased compared with those in control animals. Since tPA plays a role in synaptic plasticity, we hypothesized that tPA may contribute to the development of drug dependence. Single and repeated morphine treatment as well as repeated methamphetamine treatment induced tPA mRNA expression in the nucleus accumbens, which was associated with an increase in the enzyme activity. Conditioned place preference induced by morphine was markedly reduced in mice with a targeted deletion of the tPA gene (tPA−/− mice), being accompanied by a loss of morphine-induced dopamine release. Similarly, methamphetamine-induced conditioned place preference and locomotor sensitization were reduced in tPA −/− mice. The defects of morphine-induced hyperlocomotion as well as methamphetamine-induced locomotor sensitization in tPA−/− mice were reversed by microinjection of exogenous tPA or plasmin into the nucleus accumbens. These results support our hypothesis that tPA plays a role in long-lasting neuronal changes related to drug dependence.
- 社団法人 日本薬理学会の論文
- 2005-02-20
著者
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YAMADA Kiyofumi
Laboratory of Neuropsychopharmacology, Division of Pharmaceutical Sciences, Graduate School of Natur
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Nabeshima Toshitaka
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, J
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Yamada Kiyofumi
Laboratory Of Experimental Therapeutics Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sc
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NAGAI Taku
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science
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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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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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Nagai Taku
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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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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