Region-specific effects of developmental exposure to cocaine on fibroblast growth factor-2 expression in the rat brain
Region-specific effects of developmental exposure to cocaine on fibroblast growth factor-2 expression in the rat brain
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DOI：
10.1007/s00213-016-4315-9
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Fumagalli, Fabio
中科院分区：
文献类型：
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作者：
Giannotti, Giuseppe;Caffino, Lucia;Fumagalli, Fabio
青春期是一个极易受到滥用药物影响的时期，通过精神兴奋剂暴露改变适当的发育轨迹可能会改变生理大脑的稳态。通过打孔显微解剖大脑区域，我们调查了青少年时期反复接触可卡因是否（从出生后第28天[PND 28]到PND 42）在可卡因作用的关键脑亚区中改变了成纤维细胞生长因子-2（FGF-2）信使RNA（mRNA）水平。2腹侧被盖区（VTA）的mRNA水平，VTA是中皮层和边缘核信号通路的起源区。营养因子水平的分析显示，在远侧投射区的选择性降低FGF-2 mRNA水平的边缘下（IL）亚区的内侧前额叶皮层（中皮质途径的终端区域）和在核的核心（cNAc）（边缘通路的终端区域）。最后，我们发现FGF-2 mRNA水平在大脑区域也降低，尽管以不同的方式，有助于奖励系统，即，杏仁核中央核（cAmy）和海马体腹侧部分（vHip）。FGF-2 mRNA水平在大脑奖赏神经回路中的广泛和协调的降低可能代表了一种防御策略，以对抗可卡因的精神兴奋特性。此外，鉴于FGF-2在调节情绪障碍中的作用，这里观察到的营养支持减少可能会维持反复暴露于可卡因所引起的负面情绪状态。
Adolescence is a period of high vulnerability to drugs of abuse and alterations of the proper developmental trajectory via psychostimulant exposure might change the physiological brain homeostasis.By microdissection of brain areas via punching, we investigated whether repeated exposure to cocaine during adolescence (from postnatal day 28 [PND28] to PND42) has altered fibroblast growth factor-2 (FGF-2) messenger RNA (mRNA) levels in selected brain subregions critical for the action of cocaine.We found a reduction of FGF-2 mRNA levels in ventral tegmental area (VTA), where mesocortical and mesolimbic pathways originate. The analysis of the trophic factor levels in the distal projecting regions revealed a selective reduction of FGF-2 mRNA levels in infralimbic (IL) subregion of the medial prefrontal cortex (the terminal region of the mesocortical pathway) and in the nucleus accumbens core (cNAc) (the terminal region of the mesolimbic pathway). Last, we found reduced FGF-2 mRNA levels also in brain regions which, although in a different manner, contribute to the reward system, i.e., the central nucleus of amygdala (cAmy) and the ventral portion of hippocampus (vHip).The widespread and coordinated reduction of FGF-2 mRNA levels across the brain's reward neurocircuitry might represent a defensive strategy set in motion to oppose to the psychostimulant properties of cocaine. Moreover, given the role of FGF-2 in modulating mood disorders, the reduced trophic support here observed might sustain the negative emotional state set in motion by repeated exposure to cocaine.