Extended daily access to cocaine results in distinct alterations in Homer 1b/c and NMDA receptor subunit expression within the medial prefrontal cortex.
Extended daily access to cocaine results in distinct alterations in Homer 1b/c and NMDA receptor subunit expression within the medial prefrontal cortex.
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DOI：
10.1002/syn.20640
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发表时间：
2009-07
期刊：
影响因子：
2.3
通讯作者：
Szumlinski, Karen K.
中科院分区：
文献类型：
--
作者：
Ben-Shahar, Osnat;Obara, Ilona;Ary, Alexis W.;Ma, Natalie;Mangiardi, Mario A.;Medina, Robert L.;Szumlinski, Karen K.
人类可卡因成瘾者表现出基底节和内侧前额叶皮质(MPFC)功能的改变，这些区域内谷氨酸功能的改变被认为是可卡因成瘾的关键。本项目利用了一种高度有效的可卡因成瘾动物模型，以测试过量使用可卡因是否会改变这些脑区的谷氨酸功能。训练大鼠按压静脉注射生理盐水或可卡因(0.25 mg/次)，每天7次，每次1小时，之后，生理盐水对照组和一半的可卡因自我给药动物(短暂进入条件)再接受10次每天1小时的治疗，而其余的可卡因动物每天再接受10次6小时的治疗(延长接触条件)。在最后一次自我管理会议后1天、14天或60天，动物被处死。免疫印迹法检测腹侧被盖区(VTA)、伏隔核(N.Acc)核壳和mPFC组织中NMDA受体Hmer 1b/c、Hmer 2a/b、mGluR1、mGluR5、NR2a和NR2b亚单位的表达。短暂和长期接触可卡因未能改变VTA内的蛋白质水平，并在N.Acc蛋白表达方面产生短暂和类似的变化，这种变化在核心区更为明显。相反，长期接触可卡因导致mPFC内蛋白质表达的明显和持久的变化，包括：戒断1天Hmer 1b/c水平增加，14天NR2B水平升高，60天NR2A水平升高。这些数据支持这样一种观点，即mPFC内NMDA功能的改变可能在一定程度上有助于过渡到过度不受控制的可卡因消费。
Human cocaine addicts show altered function within the basal ganglia and the medial prefrontal cortex (mPFC) and altered glutamate function within these areas is postulated to be critical for cocaine addiction. The present project utilized a highly valid animal model of cocaine addiction, to test whether excessive use of cocaine alters glutamate function within these brain areas. Rats were trained to lever-press for IV saline vehicle or cocaine (0.25 mg/infusion) over seven 1-hr daily sessions, after which, saline controls and half of cocaine self-administering animals (brief access condition) received 10 more 1-hr daily sessions, while the remaining cocaine animals received 10 additional 6-hrs daily sessions (extended access condition). One, 14, or 60 days after the last self-administration session, animals were sacrificed. Tissue samples from the ventral tegmental area (VTA), nucleus accumbens (N.Acc) core and shell, and mPFC were analyzed by immunoblotting for expression of Homer1b/c, Homer2a/b, mGluR1, mGluR5, NR2a, and NR2b subunits of the NMDA receptor. Brief and extended access to cocaine failed to alter protein levels within the VTA, and produced transient and similar changes in N.Acc protein expression, which were more pronounced in the core subregion. In contrast, extended access to cocaine resulted in distinct and long lasting alterations of protein expression within the mPFC that included: increased levels of Homer1b/c at 1 day, NR2b at 14 days, and NR2a at 60 days, of withdrawal. These data support the notion that altered NMDA function within the mPFC may contribute, in part, to the transition to excessive uncontrolled consumption of cocaine.
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影响因子：
3.4
作者：
Ahmed, SH;Koob, GF
通讯作者：
Koob, GF
影响因子：
10.6
作者：
Franklin, TR;Acton, PD;Childress, AR
通讯作者：
Childress, AR
DOI：
10.1098/rstb.1996.0125
发表时间：
1996-10-29
影响因子：
6.3
作者：
Damasio, AR
通讯作者：
Damasio, AR
影响因子：
10.6
作者：
Ferrario, CR;Gorny, G;Robinson, TE
通讯作者：
Robinson, TE
影响因子：
3.6
作者：
Ben-Shahar, O;Moscarello, JM;Ettenberg, A
通讯作者：
Ettenberg, A