Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice.
Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice.
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MGLU5和5-HT2A受体对小鼠运动活性的相互作用。
DOI：
10.1007/s00213-010-2115-1
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发表时间：
2011-05
影响因子：
3.4
通讯作者：
Powell, Susan B.
中科院分区：
文献类型：
--
作者：
Halberstadt, Adam L.;Lehmann-Masten, Virginia D.;Geyer, Mark A.;Powell, Susan B.
代谢性谷氨酸（mGlu）受体被认为在精神分裂症、药物滥用和抑郁症等神经精神疾病中发挥作用。由于5-羟色胺能致幻剂增加谷氨酸释放和mGlu受体调节对5-羟色胺（5-HT）2A激活的反应，5-羟色胺5-HT2A受体和mGlu受体之间的相互作用可能对我们理解这些疾病很重要。我们在C57背景下测试了5-羟色胺能致幻剂、5-HT2A激动剂2,5-二甲氧基-4-甲基安非他明（DOM）和选择性5-HT2A拮抗剂M100907对mGlu5野生型（WT）和敲除型（KO）小鼠行为模式监测仪（BPM）运动活动的影响。与WT小鼠相比，雄性和雌性mGlu5 KO小鼠均表现出运动过度活跃和运动习惯减弱。同样，mGlu5阴性变构调节剂2-甲基-6-（苯乙基）吡啶（MPEP）也增加了运动亢进，而mGlu5 KO小鼠没有这种情况。DOM （0.5 mg/kg，皮下注射）可增强mGlu5受体KO小鼠的运动亢进，M100907 （1.0 mg/kg，皮下注射）可减弱其运动亢进。M100907 （0.1 mg/kg， SC）对MPEP诱导的高活性也有抑制作用。这些研究表明，mGlu5受体活性的丧失，无论是通过药理学还是通过基因缺失，都会导致小鼠运动过度活跃。此外，mGlu5受体的基因缺失增加了对5-HT2A激动剂DOM的行为反应，这表明mGlu5受体减轻了5-HT2A致幻剂的行为影响，或者mGlu5 KO小鼠对5-HT2A激动剂的敏感性增加。综上所述，这些研究表明mGlu5和5-HT2A受体之间存在功能相互作用。
Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)2A activation, the interactions between serotonin 5-HT2A receptors and mGlu receptors may prove to be important for our understanding of these diseases. We tested the effects of the serotonergic hallucinogen and 5-HT2A agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT2A antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background. Both male and female mGlu5 KO mice showed locomotor hyperactivity and diminished locomotor habituation compared with their WT counterparts. Similarly, the mGlu5-negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP) also increased locomotor hyperactivity, which was absent in mGlu5 KO mice. The locomotor hyperactivity in mGlu5 receptor KO mice was potentiated by DOM (0.5 mg/kg, subcutaneously (SC)) and attenuated by M100907 (1.0 mg/kg, SC). M100907 (0.1 mg/kg, SC) also blocked the hyperactivity induced by MPEP. These studies demonstrated that loss of mGlu5 receptor activity either pharmacologically or through gene deletion leads to locomotor hyperactivity in mice. Additionally, the gene deletion of mGlu5 receptors increased the behavioral response to the 5-HT2A agonist DOM, suggesting that mGlu5 receptors either mitigate the behavioral effects of 5-HT2A hallucinogens or that mGlu5 KO mice show an increased sensitivity to 5-HT2A agonists. Taken together, these studies indicate a functional interaction between mGlu5 and 5-HT2A receptors.
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影响因子：
5.3
作者：
Adams, B;Moghaddam, B
通讯作者：
Moghaddam, B
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作者：
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