Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core.
Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core.
复制标题
DOI：
10.1016/j.biopsych.2015.12.022
复制
发表时间：
2016-08-01
影响因子：
10.6
通讯作者：
Reissner KJ
中科院分区：
文献类型：
--
作者：
Scofield MD;Li H;Siemsen BM;Healey KL;Tran PK;Woronoff N;Boger HA;Kalivas PW;Reissner KJ
随着对神经系统功能更详细的了解，星形胶质细胞功能的多样性得到了更广泛的重视。虽然它已被证明，可卡因的经验损害星形胶质细胞谷氨酸的摄取和释放的核脑桥（NAc），很少有研究探讨了自我管理的结构和生理的星形胶质细胞的影响。我们研究了从日常可卡因自我管理对星形胶质细胞特性，包括GFAP表达，表面积，体积和共定位与突触标记物的消光的影响。可卡因或生理盐水自身给药和消退与GFAP蛋白质印迹、免疫组织化学和NAc核心星形胶质细胞的荧光成像配对（采用30只生理盐水给药和36只可卡因给药的雄性Sprague道利大鼠）。使用由GFAP启动子驱动的膜标记的Lck-GFP，结合突触蛋白I免疫组织化学进行成像。GFAP的表达显着减少，在NAc核心可卡因自我管理和灭绝。同样，我们观察到一个整体较小的表面积和体积的星形胶质细胞，以及减少共定位与突触蛋白I，在可卡因管理的动物。可卡因介导的突触接触减少被β-内酰胺抗生素头孢曲松逆转。多线的调查表明，NAc核心星形胶质细胞存在于低反应状态可卡因自我管理和灭绝。减少与突触元件的关联可能是特别有意义的，因为停止长期使用可卡因与突触强度的变化和对突触可塑性诱导的抵抗有关。我们假设星形胶质细胞突触共定位减少代表了对可卡因的重要适应不良细胞反应和复发脆弱性的潜在机制。
As a more detailed picture of nervous system function emerges, diversity of astrocyte function becomes more widely appreciated. While it has been shown that cocaine experience impairs astroglial glutamate uptake and release in the nucleus accumbens (NAc), few studies have explored effects of self-administration on the structure and physiology of astrocytes. We investigated the effects of extinction from daily cocaine self-administration on astrocyte characteristics including GFAP expression, surface area, volume, and colocalization with a synaptic marker. Cocaine or saline self-administration and extinction were paired with GFAP Westerns, immunohistochemistry, and fluorescent imaging of NAc core astrocytes (30 saline-administering and 36 cocaine-administering male Sprague Dawley rats were employed). Imaging was performed using a membrane-tagged Lck-GFP driven by the GFAP promoter, coupled with synapsin I immunohistochemistry. GFAP expression was significantly reduced in the NAc core following cocaine self-administration and extinction. Similarly, we observed an overall smaller surface area and volume of astrocytes, as well as reduced colocalization with synapsin I, in cocaine-administering animals. Cocaine-mediated reductions in synaptic contact were reversed by the β-lactam antibiotic ceftriaxone. Multiple lines of investigation indicate that NAc core astrocytes exist in a hypo-reactive state following cocaine self-administration and extinction. Decreased association with synaptic elements may be particularly meaningful, as cessation of chronic cocaine use is associated with changes in synaptic strength and resistance to the induction of synaptic plasticity. We hypothesize that the reduced synaptic colocalization of astrocytes represents an important maladaptive cellular response to cocaine and the mechanisms underlying relapse vulnerability.