The functional significance of TrkB phosphorylation in the rat nucleus accumbens as a molecular switch of habit formation in drug addiction

大鼠伏隔核TrkB磷酸化作为药物成瘾习惯形成分子开关的功能意义

• 批准号: 22591257
• 负责人: TODA Shigenobu
• 金额: $ 2.91万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591257/
• 关键词: 精神薬理学; 薬物依存; 精神薬理; 脳由来神経栄養因子; リン酸化; コカイン; 側坐核; 可塑性; TrkB; BDNF

The phosphorylations of TrkB and ribosomal protein S6 that play crucial roles in activity-dependent protein synthesis contribute to neuronal plasticity and learning/memory. In this study, we examined the effect of cocaine challenge on the important phosphorylation sites of TrkB and rpS6 in the rat nucleus accumbens after repeated saline or cocaine administration. As for TrkB, two distinct phosphorylation sites, one is required for memory acquisition, the other is for memory consolidation, were investigated. Likewise, as for rpS6, two distinct phosphorylation sites, one is mTOR-dependent, other is mTOR-independent, were examined. As a result, we found that the pattern of phosphorylation at each site was so distinctively different between control and chronic-cocaine-treated rats. N-acetylcysteine, which is supposed to restore cocaine-seeking behaviors in rodents did not provide any effect on the phosphorylations in TrkB-mTOT pathway.

TrkB和核糖体蛋白S6的磷酸化在活性依赖性蛋白质合成中起关键作用，有助于神经元的可塑性和学习/记忆。在这项研究中，我们研究了可卡因的挑战的影响，重要的磷酸化位点的TrkB和rpS 6在大鼠延髓核重复生理盐水或可卡因给药后。至于TrkB，研究了两个不同的磷酸化位点，一个是记忆获得所需的，另一个是记忆巩固所需的。同样，对于rpS 6，检测了两个不同的磷酸化位点，一个是mTOR依赖性的，另一个是mTOR非依赖性的。结果，我们发现在每个位点的磷酸化模式在对照组和慢性可卡因治疗组大鼠之间是如此明显不同。N-乙酰半胱氨酸，这是应该恢复可卡因的行为在啮齿动物没有提供任何影响的磷酸化TrkB-mTOT途径。

项目成果

Role of PSD structure sustained by action and dopamine in the rat nucleus accumbens after repeated cocaine administration.

重复给予可卡因后大鼠伏隔核中动作和多巴胺维持的 PSD 结构的作用。

• 发表时间: 2010
• 作者: Shigenobu Toda;Sakurako Kosugi;Haowei Shen;Yoshio Iguchi;Tetsu Hirosawa;Yoshio Minabe;Peter W Kalivas
• 通讯作者: Peter W Kalivas

コカイン依存における側坐核の役割;ドーパミン、グルタミン酸、そして酸化ストレス

伏隔核在可卡因依赖中的作用；多巴胺、谷氨酸和氧化应激

• 发表时间: 2011
• 作者: Shigenobu Toda;Sakurako Kosugi;Yoshio Iguchi;Yoshio Minabe;Nakao T.;戸田重誠
• 通讯作者: 戸田重誠

Differential subcellular localization of GluR1 and GluR2 in the nucleus accumbens after repeated cocaine administration;

重复给予可卡因后伏核中 GluR1 和 GluR2 的差异亚细胞定位；

• 发表时间: 2010
• 作者: Sakurako Kosugi;Yoshio Iguchi,Tetsu Hirosawa;Yoshio Minabe;Shigenobu Toda
• 通讯作者: Shigenobu Toda

Role of PSD structure sustained by action and tonic dopamine in the rat nucleus accumbens of repeatedly cocaine-administrated rats.

反复给予可卡因的大鼠伏隔核中由作用和强直多巴胺维持的 PSD 结构的作用。

• 发表时间: 2010
• 作者: Shigenobu Toda;Sakurako Kosugi;Haowei Shen;Yoshio Iguchi;Tetsu Hirosawa,Yoshio Minabe;Peter W Kalivas
• 通讯作者: Peter W Kalivas

Brain and Nerve,64: 線条体と依存症

大脑和神经，64：纹状体和成瘾

• 发表时间: 2012
• 作者: Shieenobu Toda;Sakurako Kosugi;Haowei Shen;YoshioIguchi;Tetsu Hirosawa;Yoshio Minabe;Peter W Kalivas;戸田重誠;戸田重誠
• 通讯作者: 戸田重誠