Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area.
Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area.
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DOI：
10.1007/s00213-015-4134-4
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发表时间：
2016-02
影响因子：
3.4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Kuo CC;Shen H;Harvey BK;Yu SJ;Kopajtic T;Hinkle JJ;Kyrkanides S;Katz JL;Wang Y
重复注射甲基苯丙胺（Meth）会引起行为过敏，其特征是每次注射后运动反应逐渐增加。先前的研究表明，Mu 阿片受体（MOR）可以调节冰毒介导的行为敏化。然而，所报道的相互作用是有争议的； MOR 的全身激活可以增强或抑制冰毒致敏作用。全身施用 MOR 配体后冰毒致敏的改变可能反映了多个脑区域中不同 MOR 反应的总和。本研究的目的是通过基于 AAV6 的基因传递系统区域选择性过度表达人类 MOR 后，检查 MOR 对冰毒致敏的作用。我们证明腺相关病毒 (AAV)-MOR 增加了 MOR 的体外免疫反应性和结合力。将 AAV-MOR 或 AAV-绿色荧光蛋白 (GFP) 注射到成年小鼠的伏隔核 (NAc) 或腹侧被盖区 (VTA) 中。病毒感染两周后，动物连续五天接受冰毒或盐水。测定运动行为和纹状体多巴胺 (DA) 和 3,4-二羟基苯乙酸 (DOPAC) 水平。重复服用冰毒可逐渐增强运动能力；这种致敏反应通过 NAc 内 AAV-MOR 显微注射减弱。将 AAV-MOR 输注至 VTA 增强了冰毒敏感性。 AAV-MOR 显着提高了 VTA 感染后 VTA 中的 DA 水平，但降低了 NAc 注射后 NAc 中的 DOPAC/DA 周转率。我们的数据表明，NAc 和 VTA 中 MOR 的过度表达对冰毒致敏有差异性调节。通过 AAV 区域操纵 MOR 表达可能是控制冰毒滥用和拟心理活动的一种新方法。
Repeated administration of methamphetamine (Meth) induces behavioral sensitization which is characterized by a progressive increase in locomotor response after each injection. Previous studies have shown that Mu opioid receptors (MORs) can regulate Meth-mediated behavioral sensitization. However, the reported interactions are controversial; systemic activation of MORs either enhanced or suppressed Meth sensitization. It is possible that alteration of Meth sensitization after systemic administration of MOR ligands reflects the sum of distinct MOR reactions in multiple brain regions. The purpose of the present study was to examine the actions of MORs on Meth sensitization after regionally selective overexpression of human MOR through an AAV6-based gene delivery system. We demonstrated that adeno-associated virus (AAV)-MOR increased MOR immunoreactivity and binding in vitro. AAV-MOR or AAV-green fluorescent protein (GFP) was injected into the nucleus accumbens (NAc) or ventral tegmental area (VTA) of adult mice. Two weeks after viral infection, animals received Meth or saline for five consecutive days. Locomotor behavior and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) level were determined. Repeated administration of Meth progressively increased locomotor activity; this sensitization reaction was attenuated by intra-NAc AAV-MOR microinjections. Infusion of AAV-MOR to VTA enhanced Meth sensitization. AAV-MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. Our data suggest a differential modulation of Meth sensitization by overexpression of MOR in NAc and VTA. Regional manipulation of MOR expression through AAV may be a novel approach to control Meth abuse and psychomimetic activity.
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影响因子：
3.8
作者：
Chiu, CT;Ma, TG;Ho, IK
通讯作者：
Ho, IK
DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL
影响因子：
3.3
作者：
Chou, J.;Luo, Y.;Wang, Y.
通讯作者：
Wang, Y.
影响因子：
3.4
作者：
Fang, YR;Abekawa, T;Koyama, T
通讯作者：
Koyama, T
影响因子：
4.2
作者：
HASHIMOTO, T;KODA, H;KURIYAMA, K
通讯作者：
KURIYAMA, K