A novel role for PSD-95 in mediating ethanol intoxication, drinking and place preference.
A novel role for PSD-95 in mediating ethanol intoxication, drinking and place preference.
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DOI：
10.1111/j.1369-1600.2010.00282.x
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发表时间：
2011-07
影响因子：
3.4
通讯作者：
Holmes A
中科院分区：
文献类型：
--
作者：
Camp MC;Feyder M;Ihne J;Palachick B;Hurd B;Karlsson RM;Noronha B;Chen YC;Coba MP;Grant SG;Holmes A
介导乙醇 (EtOH) 行为影响的突触信号传导机制仍然知之甚少。突触后密度 95（PSD-95、SAP-90、Dlg4）是 N-甲基-D-天冬氨酸受体 (NMDAR) 和谷氨酸突触的关键协调器，已知它们是 EtOH 行为作用的主要位点。然而，PSD-95 对 EtOH 相关行为的潜在贡献尚未确定。在这里，我们评估了缺乏 PSD-95 的敲除（KO）小鼠对 EtOH 急性中毒效应（共济失调、低温、镇静/催眠）的敏感性的多种测量，在自由获取条件下饮用 EtOH 以及剥夺、获得和长期保留 EtOH 条件性位置偏爱（CPP）（和氯化锂诱导的条件性味觉厌恶），以及对 NMDAR 拮抗剂的中毒增强反应。相对于野生型对照（WT），PSD-95 KO 对急性 EtOH 的镇静/催眠作用（但不包括共济失调或低温）表现出更高的敏感性。 PSD-95 KO 消耗的 EtOH 比 WT 少，特别是在较高的 EtOH 浓度下，尽管浓度下降和剥夺可能会导致 KO 饮用量的增加。 PSD-95 KO 在调理后 1 天表现出正常的 EtOH CPP，但在 2 周后表现出明显的厌恶。 PSD-95 KO 中氯化锂诱导的味觉厌恶在两个时间点均受到损害。最后，在测试剂量下，NMDAR 拮抗剂 MK-801 的 EtOH 增强作用在 PSD-95 KO 中完好无损。这些数据揭示了 PSD-95 在介导 EtOH 行为中的重要、新颖的作用，并进一步证明 PSD-95 是多种滥用药物影响的关键介体。
The synaptic signaling mechanisms mediating the behavioral effects of ethanol (EtOH) remain poorly understood. Post-synaptic density 95 (PSD-95, SAP-90, Dlg4) is a key orchestrator of N-methyl-D-aspartate receptors (NMDAR) and glutamatergic synapses, which are known to be major sites of EtOH’s behavioral actions. However, the potential contribution of PSD-95 to EtOH-related behaviors has not been established. Here, we evaluated knockout (KO) mice lacking PSD-95 for multiple measures of sensitivity to the acute intoxicating effects of EtOH (ataxia, hypothermia, sedation/hypnosis), EtOH drinking under conditions of free access and following deprivation, acquisition and long-term retention of EtOH conditioned place preference (CPP) (and lithium chloride-induced conditioned taste aversion), and intoxication-potentiating responses to NMDAR antagonism. PSD-95 KO exhibited increased sensitivity to the sedative/hypnotic, but not ataxic or hypothermic, effects of acute EtOH relative to wild-type controls (WT). PSD-95 KO consumed less EtOH than WT, particularly at higher EtOH concentrations, although increases in KO drinking could be induced by concentration-fading and deprivation. PSD-95 KO showed normal EtOH CPP 1 day after conditioning, but showed significant aversion 2 weeks later. Lithium chloride-induced taste aversion was impaired in PSD-95 KO at both time points. Finally, the EtOH-potentiating effects of the NMDAR antagonist MK-801 were intact in PSD-95 KO at the dose tested. These data reveal a major, novel role for PSD-95 in mediating EtOH behaviors, and add to growing evidence that PSD-95 is a key mediator of the effects of multiple abused drugs.
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DOI：
10.1523/jneurosci.4904-07.2008
发表时间：
2008-08-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hefner K;Whittle N;Juhasz J;Norcross M;Karlsson RM;Saksida LM;Bussey TJ;Singewald N;Holmes A
通讯作者：
Holmes A
影响因子：
2.9
作者：
Boyce-Rustay, Janel M.;Cameron, Heather A.;Holmes, Andrew
通讯作者：
Holmes, Andrew
多巴胺D1和D5受体基因敲除小鼠可卡因运动敏化的比较。
影响因子：
3.4
作者：
Karlsson, Rose-Marie;Hefner, Kathryn R.;Sibley, David R.;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
9.9
作者：
Fernandez, Esperanza;Collins, Mark O.;Uren, Rachel T.;Kopanitsa, Maksym V.;Komiyama, Noboru H.;Croning, Mike D. R.;Zografos, Lysimachos;Armstrong, J. Douglas;Choudhary, Jyoti S.;Grant, Seth G. N.
通讯作者：
Grant, Seth G. N.
DOI：
10.1176/appi.ajp.2010.10040484
发表时间：
2010-12
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Feyder M;Karlsson RM;Mathur P;Lyman M;Bock R;Momenan R;Munasinghe J;Scattoni ML;Ihne J;Camp M;Graybeal C;Strathdee D;Begg A;Alvarez VA;Kirsch P;Rietschel M;Cichon S;Walter H;Meyer-Lindenberg A;Grant SG;Holmes A
通讯作者：
Holmes A