Glutamatergic plasticity in medial prefrontal cortex and ventral tegmental area following extended-access cocaine self-administration.
Glutamatergic plasticity in medial prefrontal cortex and ventral tegmental area following extended-access cocaine self-administration.
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DOI：
10.1016/j.brainres.2011.06.041
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发表时间：
2011-09-21
期刊：
影响因子：
2.9
通讯作者：
Mantsch JR
中科院分区：
文献类型：
--
作者：
Ghasemzadeh MB;Vasudevan P;Giles C;Purgianto A;Seubert C;Mantsch JR
前额叶皮层和腹侧被盖区的谷氨酸信号在药物成瘾的分子和行为可塑性中起重要作用。本研究研究了可卡因自我给药后脑后内侧、腹内侧前额叶皮层和腹侧被盖区谷氨酸受体和突触支架蛋白的表达和突触后密度重分布。经过14天（每天6小时）的可卡因自我给药，大鼠暴露于三种戒断方案中的一种，持续10天。动物被关在家庭笼子里（home），回到收回杠杆的自我管理箱（Box），或者接受灭绝训练（extinction）。消失训练与显著的谷氨酸能可塑性相关。灭绝组后内侧前额叶皮层突触后GluR1、PSD95、肌动蛋白密度增加；而mGluR5受体蛋白的突触后含量下降，而NMDAR1、Homer1b/c或PICK1蛋白的含量没有变化。腹内侧前额叶皮层和腹侧被盖区未观察到这些变化。在腹侧被盖区，灭绝训练逆转了Home和Box戒断组突触后密度降低的NMDAR1蛋白。这些数据表明，药物寻求的消失与前额叶皮层和腹侧被盖区选择性谷氨酸能可塑性有关，包括受体转运到突触后密度的调节。
Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6hr/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training was associated with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of the Extinction group, there was an increase in postsynaptic density GluR1, PSD95, and actin proteins; while postsynaptic content of mGluR5 receptor protein decreased and there was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral tegmental area, Extinction training reversed the decreased postsynaptic density NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that extinction of drug seeking is associated with selective glutamatergic plasticity in prefrontal cortex and ventral tegmental area that include modulation of receptor trafficking to postsynaptic density.
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