Changes in phosphorylation of CREB, ERK, and c-fos induction in rat ventral tegmental area, hippocampus and prefrontal cortex after conditioned place preference induced by chemical stimulation of lateral hypothalamus
Changes in phosphorylation of CREB, ERK, and c-fos induction in rat ventral tegmental area, hippocampus and prefrontal cortex after conditioned place preference induced by chemical stimulation of lateral hypothalamus
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DOI：
10.1016/j.bbr.2011.01.045
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发表时间：
2011-06-20
影响因子：
2.7
通讯作者：
Hassanpour-Ezatti, Majid
中科院分区：
文献类型：
--
作者：
Haghparast, Abbas;Taslimi, Zahra;Hassanpour-Ezatti, Majid
实验证明，卡巴胆碱化学刺激大鼠下丘脑外侧区（LH）可产生条件性位置偏爱（CPP）。已有证据表明cAMP反应元件结合蛋白（CREB）、细胞外信号调节激酶（ERK）和c-fos在吗啡、可卡因、尼古丁和酒精等药物滥用诱导的CPP中起着关键作用。因此，在本研究中，我们研究了磷酸化CREB（p-CREB）和-ERK（p-ERK），和c-fos诱导腹侧被盖区（VTA），海马和前额叶皮层（PFC）收购后，由LH内注射卡巴胆碱诱导CPP的变化。通过插管将动物单侧植入LH。对于LH的化学刺激，卡巴胆碱（250 nmol/0.5 μ l生理盐水）每天显微注射一次，在CPP范例的3天调节期（采集期）。采集期后，取出脑，通过Western印迹分析测量同侧VTA、海马和PFC中的p-CREB和p-ERK以及c-fos诱导。结果表明，在LH刺激诱导的CPP过程中，VTA和PFC磷酸化CREB水平显著升高（P < 0.01和P < 0.05），而海马磷酸化CREB水平降低（P <0.05）。此外，在上述区域中，观察到c-fos水平的增加，但PFC的这种增强不显著。此外，p-ERK在这些区域发生变化，但不显著。我们的研究结果表明，研究细胞内信号及其变化，如磷酸化CREB，可以阐明LH和其他脑结构参与奖励加工在大鼠的功能关系。(C)2011 Elsevier B. V.保留所有权利。
Experimental evidence indicates that chemical stimulation of lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Several lines of evidence have shown that cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and c-fos have pivotal role in CPP induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated-CREB (p-CREB) and -ERK (p-ERK), and c-fos induction within ventral tegmental area (VTA), hippocampus and prefrontal cortex (PFC) after the acquisition of CPP induced by intra-LH administration of carbachol. Animals were unilaterally implanted by cannula into LH. For chemical stimulation of LH, carbachol (250 nmo1/0.5 mu l saline) was microinjected once each day, during 3-day conditioning phase (acquisition period) of CPP paradigm. After the acquisition period, the brains were removed, and p-CREB and p-ERK, and c-fos induction in the ipsilateral VTA, hippocampus and PFC were measured by Western blot analysis. The results indicated a significant increase in level of phosphorylated CREB (P < 0.01) in VTA, and PFC (P < 0.05), during LH stimulation-induced CPP, while its level decreased in hippocampus (P < 0.05). Also, in aforementioned regions, an increase in c-fos level was observed, but this enhancement in PFC was not significant. Moreover, p-ERK changed in these areas, but not significantly. Our findings suggest that studying the intracellular signals and their changes, such as phosphorylated-CREB, can elucidate a functional relationship between LH and other brain structures involved in reward processing in rats. (C) 2011 Elsevier B.V. All rights reserved.