کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4181209 1276643 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An Inducer for Glial Cell Line-Derived Neurotrophic Factor and Tumor Necrosis Factor–α Protects Against Methamphetamine-Induced Rewarding Effects and Sensitization
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
An Inducer for Glial Cell Line-Derived Neurotrophic Factor and Tumor Necrosis Factor–α Protects Against Methamphetamine-Induced Rewarding Effects and Sensitization
چکیده انگلیسی

BackgroundThere are few efficacious medications for drug dependence. We investigated the potential of Leu-Ile, which induces the expression of glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α), as a novel therapeutic agent for methamphetamine (METH)-induced dependence.MethodsThe levels of GDNF and TNF-α messenger RNA (mRNA) were determined by real-time reverse transcription polymerase chain reaction. Enzyme immunoassays and immunohistochemistry were employed to determine levels of these proteins. Effects of Leu-Ile on METH-induced rewarding effects and sensitization were investigated with conditioned place preference and locomotor activity tests. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were examined with an in vivo microdialysis and trititated thymidine ([3H]) DA uptake assay.ResultsLeu-Ile induced the expression of not only GDNF but also TNF-α. Pretreatment with Leu-Ile blocked the acquisition of METH-induced place preference and sensitization. Interestingly, post-treatment with Leu-Ile attenuated them even after their development. An inhibitory effect of Leu-Ile on METH-induced place preference was observed in neither GDNF heterozygous nor TNF-α knockout mice. Leu-Ile inhibited DA release in the nucleus accumbens and the decrease in synaptosomal DA uptake in the midbrain induced by repeated METH treatment.ConclusionsThese results suggest that Leu-Ile inhibits METH-induced rewarding effects and sensitization by regulating extracellular DA levels via the induction of GDNF and TNF-α expression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 61, Issue 7, 1 April 2007, Pages 890–901
نویسندگان
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