Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in rats.
Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in rats.
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DOI：
10.1371/journal.pone.0034299
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
See RE
中科院分区：
文献类型：
--
作者：
Schwendt M;Reichel CM;See RE
甲基苯丙胺（冰毒）是一种高度成瘾和广泛滥用的精神兴奋剂。反复使用冰毒会很快导致依赖，并可能伴随着各种持续的精神症状和认知障碍。慢性冰毒摄入导致的动机和认知缺陷背后的神经适应仍然知之甚少。前额叶皮层（PFC）和纹状体内谷氨酸神经传递的改变与持续的药物寻求和认知功能障碍有关。因此，目前的研究调查的变化，突触前mGluR受体皮质纹状体电路后，延长甲基自我管理。大鼠以1小时/天的时间段自我施用甲氨蝶呤（或接受轭合盐水），持续7天（短时间接触），随后是14天的6小时/天（长时间接触）。大鼠表现出每日甲基摄入量逐渐增加至每天6 mg/kg。在停止甲氨蝶呤自我给药后，大鼠在安乐死前经历14天的每日消退或禁欲而不进行消退训练。分离来自内侧PFC、中脑核（NAc）和背侧纹状体（dSTR）的突触体，并用膜不可渗透的生物素标记，以测量表面mGluR2/3和mGluR7受体。延长获得甲基自我管理，然后禁欲减少NAc和dSTR中的mGluR2/3受体的表面和总水平，而在PFC中，仅检测到表面mGluR2/3和mGluR7受体的损失。日常灭绝试验逆转了NAc中mGluR2/3受体和PFC中dSTR和mGluR7的下调，但PFC中表面mGluR2/3受体的下调与冰毒后的经历无关。因此，灭绝学习可以选择性地恢复一些群体的下调mGluRs后，长期暴露于冰毒。目前的研究结果可能对我们理解冰毒诱导的动机和认知缺陷的持续性（或恢复）有影响。
Methamphetamine (meth) is a highly addictive and widely abused psychostimulant. Repeated use of meth can quickly lead to dependence, and may be accompanied by a variety of persistent psychiatric symptoms and cognitive impairments. The neuroadaptations underlying motivational and cognitive deficits produced by chronic meth intake remain poorly understood. Altered glutamate neurotransmission within the prefrontal cortex (PFC) and striatum has been linked to both persistent drug-seeking and cognitive dysfunction. Therefore, the current study investigated changes in presynaptic mGluR receptors within corticostriatal circuitry after extended meth self-administration. Rats self-administered meth (or received yoked-saline) in 1 hr/day sessions for 7 days (short-access) followed by 14 days of 6 hrs/day (long-access). Rats displayed a progressive escalation of daily meth intake up to 6 mg/kg per day. After cessation of meth self-administration, rats underwent daily extinction or abstinence without extinction training for 14 days before being euthanized. Synaptosomes from the medial PFC, nucleus accumbens (NAc), and the dorsal striatum (dSTR) were isolated and labeled with membrane-impermeable biotin in order to measure surface mGluR2/3 and mGluR7 receptors. Extended access to meth self-administration followed by abstinence decreased surface and total levels of mGluR2/3 receptors in the NAc and dSTR, while in the PFC, only a loss of surface mGluR2/3 and mGluR7 receptors was detected. Daily extinction trials reversed the downregulation of mGluR2/3 receptors in the NAc and dSTR and mGluR7 in the PFC, but downregulation of surface mGluR2/3 receptors in the PFC was present regardless of post-meth experience. Thus, extinction learning can selectively restore some populations of downregulated mGluRs after prolonged exposure to meth. The present findings could have implications for our understanding of the persistence (or recovery) of meth-induced motivational and cognitive deficits.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
10.6
作者：
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通讯作者：
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