Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption.
Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption.
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DOI：
10.1111/jnc.12701
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发表时间：
2014-06
影响因子：
4.7
通讯作者：
Ron D
中科院分区：
文献类型：
--
作者：
Darcq E;Hamida SB;Wu S;Phamluong K;Kharazia V;Xu J;Lombroso P;Ron D
富含酪氨酸的蛋白酪氨酸磷酸酶61（STEP 61）抑制酪氨酸激酶Fyn的活性并使NMDA受体的GluN 2B亚基去磷酸化，而STEP 61的PKA磷酸化抑制磷酸酶的活性。以前，我们发现乙醇激活Fyn在背内侧纹状体（DMS）导致GluN 2B磷酸化，这反过来又是乙醇摄入量的发展的基础。在这里，我们测试了乙醇抑制STEP 61是Fyn/GluN 2B上游的假设。我们发现，小鼠暴露于乙醇增加了DMS中的STEP 61磷酸化，这在戒断后得以维持，在其他纹状体区域未观察到。特异性敲低小鼠DMS中的STEP 61增强了乙醇介导的Fyn激活和GluN 2B磷酸化，并增加了乙醇摄入量，而不改变水，糖精，奎宁消耗或自发运动活性的水平。总之，我们的数据表明，阻断响应乙醇的STEP 61活性足以激活DMS中的Fyn/GluN 2B通路。作为Fyn和GluN 2B的上游，DMS中的无活性STEP 61引发乙醇摄入的诱导。
The STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) inhibits the activity of the tyrosine kinase Fyn and dephosphorylates the GluN2B subunit of the NMDA receptor, whereas PKA phosphorylation of STEP61 inhibits the activity of the phosphatase. Previously, we found that ethanol activates Fyn in the dorsomedial striatum (DMS) leading to GluN2B phosphorylation, which, in turn, underlies the development of ethanol intake. Here, we tested the hypothesis that inhibition of STEP61 by ethanol is upstream of Fyn/GluN2B. We show that exposure of mice to ethanol increased STEP61 phosphorylation in the DMS, which was maintained after withdrawal and was not observed in other striatal regions. Specific knockdown of STEP61 in the DMS of mice enhanced ethanol-mediated Fyn activation and GluN2B phosphorylation, and increased ethanol intake without altering the level of water, saccharine, quinine consumption or spontaneous locomotor activity. Together, our data suggest that blockade of STEP61 activity in response to ethanol is sufficient for the activation of the Fyn/GluN2B pathway in the DMS. Being upstream of Fyn and GluN2B, inactive STEP61 in the DMS primes the induction of ethanol intake.
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影响因子：
4.7
作者：
Gibb SL;Hamida SB;Lanfranco MF;Ron D
通讯作者：
Ron D
DOI：
10.1016/0169-328x(95)00066-2
发表时间：
1995-08-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
SHARMA, E;ZHAO, FS;LOMBROSO, PJ
通讯作者：
LOMBROSO, PJ
DOI：
10.1073/pnas.1017856108
发表时间：
2011-04-19
影响因子：
11.1
作者：
Hicklin, Tianna R.;Wu, Peter H.;Browning, Michael D.
通讯作者：
Browning, Michael D.
影响因子：
3.4
作者：
Braithwaite, Steven P.;Adkisson, Michael;Nikolich, Karoly
通讯作者：
Nikolich, Karoly
影响因子：
4.8
作者：
Suvarna, N;Borgland, SL;Ron, D
通讯作者：
Ron, D