NrCAM-regulating neural systems and addiction-related behaviors.
NrCAM-regulating neural systems and addiction-related behaviors.
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DOI：
10.1111/j.1369-1600.2012.00469.x
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发表时间：
2014-05
影响因子：
3.4
通讯作者：
Arinami T
中科院分区：
文献类型：
--
作者：
Ishiguro H;Hall FS;Horiuchi Y;Sakurai T;Hishimoto A;Grumet M;Uhl GR;Onaivi ES;Arinami T
我们之前已经证明，与大脑中NrCAM表达减少相关的单倍型可以保护人类免受多物质滥用的成瘾脆弱性，并且NrCAM敲除小鼠不会对吗啡、可卡因或苯丙胺产生条件性位置偏好。为了深入了解NrCAM参与成瘾的脆弱性，这可能涉及特定的神经回路相关的成瘾行为特征，我们评估了几个行为表型NrCAM基因敲除小鼠。与动机功能的潜在普遍降低一致，Nrcam敲除小鼠对新物体和不熟悉的同种表现出较少的好奇心，在零迷宫中也表现出较少的焦虑。Nrcam杂合子敲除小鼠减少了酒精偏好，并在家中笼子里埋了更少的大理石。这些观察结果提供了进一步的支持NrCAM在药物滥用，包括酗酒的脆弱性，可能通过其对行为特征的影响，可能会影响成瘾的脆弱性，包括新奇的寻求，强迫症和厌恶或焦虑引起的刺激的反应的作用。此外，为了证实成瘾的谷氨酸稳态假说，我们分析了NRCAM调控的谷氨酸能分子。谷氨酰胺酶在人和小鼠两种不同组织中参与NrCAM相关的分子通路。一种酶的抑制剂，PLG，治疗产生了，至少，在酒精偏好和焦虑样行为中显示的小鼠的一些表型。因此，NrCAM可以通过至少部分调节大脑中的某些谷氨酸能通路和神经功能来影响成瘾相关行为。
We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine, or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM. Glutaminase appears to be involved in NrCAM-related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, PLG, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partial modulation of some glutamatargic pathways and neural function in brain.
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影响因子：
2
作者：
Gerra, G.;Bertacca, S.;Ferri, M.
通讯作者：
Ferri, M.
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2.5
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Hall, FS;Li, XF;Uhl, GR
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DELACOUR, J
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Kostowski, W
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Lukasiewicz, Michael;Neveu, Xavier;Gasquet, Isabelle
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