Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of P rats.
Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of P rats.
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DOI：
10.1111/j.1530-0277.2009.01030.x
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Obara I;Bell RL;Goulding SP;Reyes CM;Larson LA;Ary AW;Truitt WA;Szumlinski KK
Homer蛋白是调节中心组1代谢性谷氨酸受体（mGluRs）和n -甲基- d -天冬氨酸（NMDA）受体的运输和功能的支架复合物的组成部分。研究支持这些蛋白参与乙醇诱导的小鼠神经可塑性。在这项研究中，我们研究了短期和长期戒酒对选择性饲养的酒精偏好P大鼠纹状体和杏仁核亚区荷马和谷氨酸受体蛋白表达的影响。在6个月的时间里，雄性P大鼠在家中的笼子里，在间歇（IA: 4 d/周）或连续（CA: 7 d/周）的条件下同时摄入15%和30%的乙醇溶液。在终止乙醇接触后24小时（短停药：SW）或4周（长停药：LW）处死大鼠，对感兴趣的亚区进行微孔处理，并对组织进行检测Group1 mGluRs、NMDA受体NR2亚基和Homer蛋白表达。在伏隔核（NAC）中，壳（NACsh）中NR2a和NR2b的表达变化有限，而核心（NACc）中Homer2a/b、mGluRs以及NR2a和NR2b亚基的表达变化明显。在杏仁核内，基底外侧亚区未检测到变化，而在中央核（CeA）亚区检测到许多与NACc相似的实质性变化。此外，在SW和LW大鼠中观察到的大部分CeA变化，而非NACc。总的来说，这些亚区域特异性，乙醇诱导的NAC和杏仁核中mGluR/Homer2/NR2表达的增加表明谷氨酸能可塑性发生了变化。这可能是学习和随后的记忆形成的结果，乙醇的奖励作用在这些大脑结构中，这可能部分地介导了酒精滥用的慢性复发性质。
Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N-methyl-D-aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse. In this study, we examined the effects of short versus long-term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol-preferring P rats. For 6 months, male P rats had concurrent access to 15% and 30% ethanol solutions under intermittent (IA: 4 d/wk) or continuous (CA: 7 d/wk) access conditions in their home cage. Rats were killed 24 hours (short withdrawal: SW) or 4 weeks (long withdrawal: LW) after termination of ethanol access, subregions of interest were micropunched and tissue processed for detection of Group1 mGluRs, NR2 subunits of the NMDA receptor and Homer protein expression. Within the nucleus accumbens (NAC), limited changes in NR2a and NR2b expression were detected in the shell (NACsh), whereas substantial changes were observed for Homer2a/b, mGluRs as well as NR2a and NR2b subunits in the core (NACc). Within the amygdala, no changes were detected in the basolateral subregion, whereas substantial changes, many paralleling those observed in the NACc, were detected in the central nucleus (CeA) subregion. In addition, most of the changes observed in the CeA, but not NACc, were present in both SW and LW rats. Overall, these subregion specific, ethanol-induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol’s rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse.
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