Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.
Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.
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DOI：
10.1016/j.neuropharm.2017.10.010
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发表时间：
2018-01
影响因子：
4.7
通讯作者：
Piepponen TP
中科院分区：
文献类型：
--
作者：
Kopra J;Villarta-Aguilera M;Savolainen M;Weingerl S;Myöhänen TT;Rannanpää S;Salvatore MF;Andressoo JO;Piepponen TP
成瘾性药物会增强纹状体中多巴胺的释放，这可能导致反复接触后的强迫性药物寻求。胶质细胞源性神经营养因子（GDNF）是中脑多巴胺能神经元的重要调节因子，可能在成瘾相关行为中发挥机制性作用。为了阐明GDNF信号的组成部分，有助于成瘾相关的位置偏爱行为及其灭绝，我们利用两个转基因GDNF小鼠模型在安非他明诱导的条件性位置偏爱（CPP）的范例，并评估行为的发现与多巴胺信号在背侧和腹侧纹状体。我们利用两种基因敲入小鼠品系来描绘GDNF和Ret信号传导的贡献，使用MEN2B小鼠（组成型活性GDNF受体Ret）和GDNF超形态小鼠（增强的内源性GDNF表达）。安非他明诱导的CPP的持续时间在MEN2B小鼠中大大增加，但在GDNF高形态小鼠中没有。CPP的增强持续时间与腹侧纹状体中酪氨酸羟化酶（TH）表达和多巴胺含量的增加相关。总之，我们的研究结果表明，GDNF信号传导的下游成分，在这种情况下，Ret，可能通过增加中脑边缘多巴胺神经元中的TH表达和多巴胺水平来介导持续的药物寻求行为。
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.
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影响因子：
2.5
作者：
FALLON, JH;MOORE, RY
通讯作者：
MOORE, RY
成瘾神经生物学和未来方向的神经营养因素的更新。
影响因子：
6.1
作者：
Koskela, Maryna;Back, Susanne;Voikar, Vootele;Richie, Christopher T.;Domanskyi, Andrii;Harvey, Brandon K.;Airavaara, Mikko
通讯作者：
Airavaara, Mikko
影响因子：
3.7
作者：
Salvatore MF;Pruett BS
通讯作者：
Pruett BS
影响因子：
3.4
作者：
Airavaara, M;Planken, A;Ahtee, L
通讯作者：
Ahtee, L
影响因子：
56.9
作者：
LIN, LFH;DOHERTY, DH;COLLINS, F
通讯作者：
COLLINS, F