Adolescent cocaine exposure induces prolonged synaptic modifications in medial prefrontal cortex of adult rats.
Adolescent cocaine exposure induces prolonged synaptic modifications in medial prefrontal cortex of adult rats.
复制标题
青少年接触可卡因会引起成年大鼠内侧前额叶皮质的长期突触改变。
DOI：
10.1007/s00429-017-1590-0
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Guan X
中科院分区：
文献类型：
--
作者：
Zhu W;Ge X;Gao P;Li M;Guan Y;Guan X
在青少年时期使用的物质增加了以后生活中精神疾病的风险，但潜在的神经机制仍不清楚。我们推测，青少年可卡因暴露后内侧前额叶皮层（mPFC）的突触重塑和稳态变化可能会持续很长一段时间，这些变化可能导致成年后的行为缺陷。为了解决这一假设，大鼠暴露于可卡因盐酸盐从出生后第28天（P28）至P42。当老鼠长大成人后，他们对老鼠进行了行为测试。在P75和P76，可卡因经验的大鼠表现出增加的运动和焦虑样行为，以及受损的非选择性注意。在可卡因经验的大鼠，突触相关蛋白（synapsin I和PSD-95）的水平和突触和树突棘的密度与对照组相比，均显着下降。出乎意料的是，与氧化应激、炎症和凋亡相关的分子的表达在青少年可卡因暴露后的mPFC中没有显着变化。这些结果表明，青少年接触可卡因诱导mPFC突触的长期修饰，这可能有助于成年后的长期行为结果。
Substance used during adolescent period increases the risk of psychiatric disorders in later life, but the underlying neural mechanisms remain unclear. We hypothesize that synaptic remodeling and changes of homeostasis in the medial prefrontal cortex (mPFC) following adolescent cocaine exposure may last for a long time, and these modifications may contribute to behavioral deficiencies in adulthood. To address this hypothesis, rats were exposed to cocaine hydrochloride from postnatal day 28 (P28) to P42. When reared to adulthood, rats were subjected to behavioral tests. On P75 and P76, cocaine-experienced rats exhibited increased locomotive and anxiety-like behaviors, as well as impaired non-selective attention. In the cocaine-experienced rats, both levels of synapse-related proteins (synapsin I and PSD-95) and density of synapse and dendrite spine in mPFC were significantly decreased when compared to controls. Unexpected, the expression of molecules related to oxidative stress, inflammation and apoptosis showed no significant changes in mPFC following adolescent cocaine exposure. These findings suggested that adolescent exposure to cocaine induce long-term modification on synapses in mPFC, which might contribute to long-term behavioral outcomes in adulthood.