Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit
Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit
复制标题
DOI：
10.1007/s00213-006-0448-6
复制
发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Holmes, Andrew
中科院分区：
文献类型：
--
作者：
Boyce-Rustay, Janel M.;Holmes, Andrew
基本原理 离子型 NMDA 谷氨酸受体由 NR1 和 NR2 (NR2A-D) 亚基组成。虽然有令人信服的证据表明 NMDA 受体调节乙醇的行为效应，但人们对 NMDA 受体的亚基组成如何介导这些效应知之甚少。 目的 在本研究中，我们通过对 NR2A 敲除 (KO) 小鼠中乙醇相关行为的表型评估来评估 NMDA 亚基的相对作用。 结果 结果表明 NR2A KO 和 杂合子小鼠未能表现出乙醇诱导的条件性位置偏好的证据。与野生型 (WT) 对照相比，KO 小鼠在基线时表现出运动协调受损，在某些情况下，在加速旋转棒、平衡木和吊线测试中接受乙醇治疗后，KO 小鼠表现出运动协调受损。相比之下，基因型之间对乙醇的开放场运动刺激、镇静/催眠和低温反应没有差异，两瓶选择范式中的自愿乙醇消耗和偏好也没有差异。腹腔注射乙醇后，KO 小鼠的血液乙醇浓度低于 WT 小鼠。 结论 结果表明，含有 NR2A 亚基的 NMDA 受体的缺失会损害形成或表达对乙醇的习得奖赏相关反应的能力，并导致运动协调缺陷。然而，NR2A 的缺失并不会改变急性乙醇中毒或乙醇消耗的其他指标，这可能表明其他 NMDA 亚基也参与了这些影响。这些数据为 NMDA 受体在调节乙醇行为效应中的作用提供了新的见解。
Rationale The ionotropic NMDA glutamate receptor is composed of NR1 and NR2 (NR2A-D) subunits. While there is compelling evidence that NMDA receptors modulate behavioral effects of ethanol, there is little understanding of how the subunit composition of the NMDA receptor mediates these effects.Objectives In the current study, we assessed the relative roles of NMDA subunits via phenotypic assessment of ethanol-related behaviors in NR2A knockout (KO) mice.Results Results demonstrated that NR2A KO and heterozygous mice failed to show evidence of ethanol-induced conditioned place preference. As compared to wild-type (WT) controls, KO mice showed impaired motor coordination at baseline and, in some instances, following ethanol treatment on the accelerating rotarod, balance beam, and wire-hang tests. By contrast, open field locomotor-stimulant, sedative/hypnotic, and hypothermic responses to ethanol were not different between genotypes, nor was voluntary ethanol consumption and preference in a two-bottle choice paradigm. Blood ethanol concentrations were lower in KO than WT mice following intraperitoneal ethanol injection.Conclusions Results suggest that the loss of NR2A subunit-containing NMDA receptors impairs the ability to form or express learned reward-related responses to ethanol and causes deficits in motor coordination. However, the loss of NR2A does not alter other measures of acute ethanol intoxication or ethanol consumption, possibly implicating other NMDA subunits in these effects. These data provide novel insight into the role of NMDA receptors in modulating the behavioral effects of ethanol.