کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998247 | 1115614 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The immunophilin ligand FK506 protects against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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![عکس صفحه اول مقاله: The immunophilin ligand FK506 protects against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum The immunophilin ligand FK506 protects against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum](/preview/png/8998247.png)
چکیده انگلیسی
Repeated use of methamphetamine (MAP) is known to cause neurotoxicity in the dopaminergic neurons of the striatum. Recently, we reported that FK506, a calcineurin inhibitor and immunosuppressive agent, could attenuate acute behavioral changes and the development of sensitization after administration of MAP. In this study, we investigated the effects of FK506 on the neurotoxicity in the dopaminergic neurons induced by repeated administration of MAP. BALB/c mice were injected subcutaneously (s.c.) with vehicle (10Â ml/kg) or MAP (4Â mg/kg) four times every 2Â h. Vehicle (10Â ml/kg) or FK506 (0.1, 0.3, 1 or 3Â mg/kg i.p.) was administered 15Â min before the first MAP administration. Three days later, we assessed the contents of dopamine (DA) and its major metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the mouse striatum using high-performance liquid chromatography (HPLC). We also examined the immunohistochemistry of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the mouse brain. Repeated administration of MAP decreased significantly the contents of DA and DOPAC in the mouse striatum, and pretreatment with FK506 inhibited significantly the reduction of DA and DOPAC in the mouse brain by repeated administration of MAP. Furthermore, repeated administration of MAP decreased significantly the immunoreactivity of DAT and TH in the striatum as compared to controls. Pretreatment with FK506 (3Â mg/kg) attenuated significantly the reduction of DAT and TH immunoreactivity after repeated administration of MAP. These results suggest that FK506 shows protective effects on the MAP-induced neurotoxicity in the dopaminergic neurons of the mouse striatum.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 48, Issue 3, March 2005, Pages 391-397
Journal: Neuropharmacology - Volume 48, Issue 3, March 2005, Pages 391-397
نویسندگان
Kaori Koike, Kenji Hashimoto, Goro Fukami, Naoe Okamura, Lin Zhang, Shintaro Ohgake, Hiroki Koizumi, Daisuke Matsuzawa, Noriyuki Kawamura, Eiji Shimizu, Masaomi Iyo,