دانلود مقاله ISI انگلیسی شماره 136013
ترجمه فارسی عنوان مقاله

سیگنالینگ ثابت مجدد منجر به بیان طولانی مدت تهویه مطبوع از طریق مکان یابی ناشی از آمفتامین با افزایش دوپامین مازولیمبیک

عنوان انگلیسی
Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine
کد مقاله سال انتشار تعداد صفحات مقاله انگلیسی
136013 2018 34 صفحه PDF
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Neuropharmacology, Volume 128, January 2018, Pages 221-230

پیش نمایش مقاله
پیش نمایش مقاله  سیگنالینگ ثابت مجدد منجر به بیان طولانی مدت تهویه مطبوع از طریق مکان یابی ناشی از آمفتامین با افزایش دوپامین مازولیمبیک

چکیده انگلیسی

Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.