Measures of anxiety, sensorimotor function, and memory in male and female mGluR4⁻/⁻ mice.
Measures of anxiety, sensorimotor function, and memory in male and female mGluR4⁻/⁻ mice.
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DOI：
10.1016/j.bbr.2011.12.037
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发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Raber, Jacob
中科院分区：
文献类型：
--
作者：
Davis, Matthew J.;Haley, Tammie;Duvoisin, Robert M.;Raber, Jacob
代谢型谷氨酸受体（mGluRs）通过G蛋白与第二信使途径偶联并调节突触传递。在八种不同类型的mGluR（mGluR 1-mGluR 8）中，mGluR 4、mGluR 6、mGluR 7和mGluR 8是组III的成员。III组受体通常位于突触前，在那里它们调节神经递质的释放。由于它们在调节神经传递中的作用，mGluRs是旨在治疗焦虑症的疗法的有吸引力的靶标。先前我们表明，mGluR 4选择性变构激动剂VU 0155041减少野生型雄性小鼠的焦虑样行为。在这里，我们探讨了mGluR 4在缺乏这种受体的成年（6个月大）和中年（12个月大）雄性和雌性小鼠中的作用。与年龄和性别匹配的野生型小鼠相比，中年mGluR 4-/-雄性小鼠在旷场和升高的零迷宫中表现出增加的焦虑程度，并在旋转棒上表现出感觉运动功能受损。这些变化在6个月大的成年雄性小鼠中未观察到。与雄性小鼠相比，mGluR 4-/-雌性小鼠在旷场和升高的零迷宫中显示出降低的焦虑测量值和增强的旋转棒性能。在水迷宫的隐藏平台训练期间，mGluR 4-/-小鼠在6个月大时比野生型小鼠游得更远，但在12个月大时没有。mGluR 4-/-小鼠也表现出增强的杏仁核依赖性线索恐惧条件反射。没有基因型差异被认为是依赖于校园的背景恐惧条件反射。这些数据表明，mGluR 4对感觉运动功能和焦虑措施的影响，但不提示恐惧条件反射，受到性别和年龄的严重调制。
Metabotropic glutamate receptors (mGluRs) are coupled to second messenger pathways via G proteins and modulate synaptic transmission. Of the eight different types of mGluRs (mGluR1-mGluR8), mGluR4, mGluR6, mGluR7, and mGluR8 are members of group III. Group III receptors are generally located presynaptically, where they regulate neurotransmitter release. Because of their role in modulating neurotransmission, mGluRs are attractive targets for therapies aimed at treating anxiety disorders. Previously we showed that the mGluR4-selective allosteric agonist VU 0155041 reduces anxiety-like behavior in wild-type male mice. Here, we explore the role of mGluR4 in adult (6-month-old) and middle-aged (12-month-old) male and female mice lacking this receptor. Compared to age- and sex-matched wild-type mice, middle-aged mGluR4-/- male mice showed increased measures of anxiety in the open field and elevated zero maze and impaired sensorimotor function on the rotarod. These changes were not seen in adult 6-month old male mice. In contrast to the male mice, mGluR4-/- female mice showed reduced measures of anxiety in the open field and elevated zero maze and enhanced rotarod performance. During the hidden platform training sessions of the water maze, mGluR4-/-mice swam father away from the platform than wild-type mice at 6, but not at 12, months of age. mGluR4-/- mice also showed enhanced amygdala-dependent cued fear conditioning. No genotype differences were seen in hippocampus-dependent contextual fear conditioning. These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age.
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影响因子：
4.7
作者：
Linden, AM;Johnson, BG;Schoepp, DD
通讯作者：
Schoepp, DD
影响因子：
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作者：
Corti, C;Aldegheri, L;Ferraguti, F
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Ferraguti, F
影响因子：
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Hopkins CR;Lindsley CW;Niswender CM
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Niswender CM
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作者：
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通讯作者：
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作者：
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