Testen Anze, Sepulveda-Orengo Marian T, Gaines Christiann H, Reissner Kathryn J
Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Front Cell Neurosci. 2018 Aug 7;12:246. doi: 10.3389/fncel.2018.00246. eCollection 2018.
While much is known about the effects of cocaine use on the cellular structure and function of neurons and synapses within the brain's reward circuitry, relatively little is known about the effects of cocaine on astrocytes. Given the significant role that astrocytes play in modulating neuronal and synaptic function, this lack of knowledge regarding the role of astroglial adaptations in the neuropathology of drug abuse represents an important investigative need. We recently showed that astrocytes within the nucleus accumbens (NAc) core exhibit decreased volume, surface area, and synaptic colocalization following cocaine self-administration and extinction, compared to NAc astrocytes from saline-administering animals (Scofield et al., 2016b). However, it is unknown whether these cocaine-dependent changes in astrocytes are ubiquitous throughout the brain's reward circuitry, or represent specific adaptations within the NAc. It is also not known whether the extinction period is necessary for the retracted phenotype, or whether self-administration alone is sufficient to drive these changes. In the current study, we have extended our assessment of the effects of cocaine self-administration on morphometric properties and synaptic colocalization of astrocyte peripheral processes in the prelimbic region of the medial prefrontal cortex (PL) and basolateral nucleus of the amygdala (BLA), both known to also contribute significantly to motivated behaviors. In addition, in order to pinpoint the temporal dimension of previously observed effects, we also examined astrocytes within the NAc following the last self-administration session. While a reduction of astrocyte size and synaptic colocalization was observed in the NAc core of cocaine-extinguished rats as previously shown, no differences in PL or BLA astrocytes were observed between saline- and cocaine-extinguished rats. Moreover, decreased synaptic colocalization of peripheral processes in the NAc was observed with a post-synaptic marker, instead of a presynaptic marker as used previously. In contrast, no significant changes were found in NAc astrocytes after self-administration alone. These results provide insights into the influence of cocaine use on astrocytes within the brain reward circuitry, and inform both regional heterogeneity as well as temporal dynamics of astrocyte responsiveness to cocaine self-administration.
虽然人们对可卡因使用对大脑奖赏回路中神经元和突触的细胞结构及功能的影响了解甚多，但对可卡因对星形胶质细胞的影响却知之甚少。鉴于星形胶质细胞在调节神经元和突触功能方面发挥着重要作用，目前对于星形胶质细胞适应性变化在药物滥用神经病理学中的作用缺乏了解，这表明有必要进行重要的研究。我们最近发现，与给予生理盐水的动物伏隔核（NAc）核心中的星形胶质细胞相比，可卡因自我给药和消退后，伏隔核核心中的星形胶质细胞体积、表面积和突触共定位减少（斯科菲尔德等人，2016b）。然而，尚不清楚这些可卡因依赖的星形胶质细胞变化是否在整个大脑奖赏回路中普遍存在，还是仅代表伏隔核内的特定适应性变化。也不清楚消退期对于星形胶质细胞收缩表型是否必要，或者仅自我给药是否足以驱动这些变化。在本研究中，我们扩展了对可卡因自我给药对内侧前额叶皮质（PL）前边缘区和杏仁核基底外侧核（BLA）中星形胶质细胞外周突起的形态学特性和突触共定位影响的评估，已知这两个区域对动机行为也有显著贡献。此外，为了确定先前观察到的效应的时间维度，我们还在最后一次自我给药后检查了伏隔核内的星形胶质细胞。正如先前所示，在可卡因消退大鼠的伏隔核核心中观察到星形胶质细胞大小和突触共定位减少，但在给予生理盐水和可卡因消退的大鼠之间，PL或BLA星形胶质细胞未观察到差异。此外，使用突触后标记物而非先前使用的突触前标记物观察到伏隔核中外周突起的突触共定位减少。相比之下，仅自我给药后伏隔核星形胶质细胞未发现显著变化。这些结果为可卡因使用对大脑奖赏回路中星形胶质细胞的影响提供了见解，并揭示了星形胶质细胞对可卡因自我给药反应的区域异质性和时间动态。
