Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats.
Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats.
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DOI：
10.1111/adb.12504
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
McGinty JF
中科院分区：
文献类型：
--
作者：
Siemsen BM;Lombroso PJ;McGinty JF
大鼠自我注射可卡因会导致早期戒断期间前边缘 (PrL) 皮质的神经适应功能障碍。这些适应的核心是磷酸细胞外信号调节激酶（p-ERK）的减少，它在可卡因寻求中发挥着关键作用。可卡因自我给药后立即使 PrL 皮质中的 ERK 磷酸化正常化可减少随后的可卡因寻求。 ERK 磷酸化的紊乱伴随着纹状体富含蛋白酪氨酸磷酸酶 (STEP) 的磷酸化降低，表明 STEP 活性增加。 STEP 是一种公认的 ERK 磷酸酶，但早期戒断期间 STEP 激活是否介导 p-ERK 减少并参与复发尚不清楚。在这里，我们表明，在自我给药后立即进行选择性STEP抑制剂TC-2153的单次PrL皮质内微量输注可以抑制戒断后环境诱导的在灭绝条件下的复发和提示诱导的恢复，但不能抑制可卡因引发的药物寻求或蔗糖寻求。此外，自我给药后立即进行 PrL 皮质内 TC-2153 微量输注可防止早期戒断期间可卡因诱导的 PrL 皮质内 p-ERK 的减少。有趣的是，在同一时间点全身注射 TC-2153 未能抑制戒断后环境诱导的复发或提示诱导的恢复，但确实抑制了可卡因引发的恢复。这些数据表明，早期戒断期间，STEP 诱导的 PrL 皮层中的 ERK 去磷酸化是促进可卡因寻求复发的关键神经适应，并且早期戒断期间 STEP 的全身性抑制与 PrL 皮层内抑制可差异性地抑制可卡因寻求。
Cocaine self-administration in rats results in dysfunctional neuroadaptations in the prelimbic (PrL) cortex during early abstinence. Central to these adaptations is decreased phospho-extracellular signal-regulated kinase (p-ERK), which plays a key role in cocaine-seeking. Normalizing ERK phosphorylation in the PrL cortex immediately after cocaine self-administration decreases subsequent cocaine-seeking. The disturbance in ERK phosphorylation is accompanied by decreased phosphorylation of striatal-enriched protein tyrosine phosphatase (STEP), indicating increased STEP activity. STEP is a well-recognized ERK phosphatase but whether STEP activation during early abstinence mediates the decrease in p-ERK and is involved in relapse is unknown. Here we show that a single intra-PrL cortical microinfusion of the selective STEP inhibitor, TC-2153, immediately after self-administration suppressed post-abstinence context-induced relapse under extinction conditions and cue-induced reinstatement, but not cocaine prime-induced drug-seeking or sucrose-seeking. Moreover, an intra-PrL cortical TC-2153 microinfusion immediately after self-administration prevented the cocaine-induced decrease in p-ERK within the PrL cortex during early abstinence. Interestingly, a systemic TC-2153 injection at the same time point failed to suppress post-abstinence context-induced relapse or cue-induced reinstatement, but did suppress cocaine prime-induced reinstatement. These data indicate that the STEP-induced ERK dephosphorylation in the PrL cortex during early abstinence is a critical neuroadaptation that promotes relapse to cocaine-seeking and that systemic versus intra-PrL cortical inhibition of STEP during early abstinence differentially suppresses cocaine-seeking.
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影响因子：
4.6
作者：
Tian M;Xu J;Lei G;Lombroso PJ;Jackson MF;MacDonald JF
通讯作者：
MacDonald JF
影响因子：
9.8
作者：
Xu J;Chatterjee M;Baguley TD;Brouillette J;Kurup P;Ghosh D;Kanyo J;Zhang Y;Seyb K;Ononenyi C;Foscue E;Anderson GM;Gresack J;Cuny GD;Glicksman MA;Greengard P;Lam TT;Tautz L;Nairn AC;Ellman JA;Lombroso PJ
通讯作者：
Lombroso PJ
影响因子：
4.7
作者：
Paul S;Connor JA
通讯作者：
Connor JA
抑制酪氨酸磷酸酶Step61可恢复BDNF的表达，并逆转苯基二酮治疗小鼠的运动和认知缺陷。
DOI：
10.1007/s00018-015-2057-1
发表时间：
2016-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Xu J;Kurup P;Baguley TD;Foscue E;Ellman JA;Nairn AC;Lombroso PJ
通讯作者：
Lombroso PJ
影响因子：
3.4
作者：
Braithwaite, Steven P.;Adkisson, Michael;Nikolich, Karoly
通讯作者：
Nikolich, Karoly