Nucleus accumbens long-term depression and the expression of behavioral sensitization
Nucleus accumbens long-term depression and the expression of behavioral sensitization
复制标题
DOI：
10.1126/science.1116894
复制
发表时间：
2005-11-25
期刊：
影响因子：
56.9
通讯作者：
Wang, YT
中科院分区：
文献类型：
--
作者：
Brebner, K;Wong, TP;Wang, YT
与药物成瘾和精神分裂症相关的药物依赖性神经可塑性可以在动物中建模为行为敏化，其由重复非偶然或自我施用许多滥用药物引起。对行为致敏至关重要的分子机制尚未明确。已提出脑中α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸受体（AMPAR）介导的突触传递的长期抑制（LTD）作为学习和记忆的细胞底物。LTD在突触后核（NAc）的表达需要网格蛋白依赖的AMPAR的内吞作用。NAc LTD被动力蛋白衍生的肽阻断，该肽抑制网格蛋白介导的内吞作用，或被GluR 2衍生的肽阻断调节的AMPAR内吞作用。全身或内NAc输注的膜渗透性GluR 2肽防止安非他明诱导的行为敏化大鼠的表达。
Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs of abuse. Molecular mechanisms that are critical for behavioral sensitization have yet to be specified. Long-term depression (LTD) of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)-mediated synaptic transmission in the brain has been proposed as a cellular substrate for learning and memory. The expression of LTD in the nucleus accumbens (NAc) required clathrin-dependent endocytosis of postsynaptic AMPARs. NAc LTD was blocked by a dynamin-derived peptide that inhibited clathrin-mediated endocytosis or by a GluR2-derived peptide that blocked regulated AMPAR endocytosis. Systemic or intra-NAc infusion of the membrane-permeable GluR2 peptide prevented the expression of amphetamine-induced behavioral sensitization in the rat.