文章基本信息

标题：Molecular changes in the medial prefrontal cortex and nucleus accumbens are associated with blocking the behavioral sensitization to cocaine
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作者：Yi Zhang ; Xiongzhao Zhu ; Can Huang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep16172
语种：English
出版社：Springer Nature
摘要：Previous studies have demonstrated that cocaine-induced behavioral sensitization is associated with persistent functional and structural alterations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc); however, the molecular mechanisms underlying these changes have not been elucidated. In this study, the behavioral sensitization to cocaine was established in Sprague Dawley rats and was measured by locomotion and behavioral rating. The brain tissue homogenization was used for measuring the level of brain-derived neurotrophic factor (BDNF), the expression and activity of integrin-linked kinase (ILK), level of protein kinase B (Akt) phosphorylation at serine 473 and threonine 308, and the expression of p75^NTR, TrkA, and TrkB protein. The Results showed that cocaine sensitization was associated with increased BDNF, ILK activity, phospho-Akt Ser⁴⁷³, p75^NTR, and TrkB protein levels in the mPFC and NAc core. The combination of pergolide and ondansetron normalized not only behavioral sensitization, but also the increases in these molecular markers. Dual immunofluoresence staining showed that ILK expression is co-distributed with p75^NTR and TrkA expression in both the mPFC and NAc core. Results suggested that the BDNF-TrkA/p75^NTR-ILK-Akt signaling pathway may be active in cocaine sensitization and associated neural plasticity in the mPFC and NAc core.