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Increased sensitivity to psychostimulants and GABAergic drugs in Lsamp-deficient mice

机译:在Lsamp缺陷小鼠中增加了对精神疗递和胃肠杆菌药物的敏感性

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摘要

Lsamp, in combinations with other members of the IgLON family of cell adhesion molecules, promotes and inhibits neurite outgrowth and synapse formation during development. Mice lacking Lsamp gene display decreased social behaviour, hyperactivity; decreased anxiety level, alongside with altered balance in GABAA receptor alpha 1 and alpha 2 subunits; and decreased sensitivity to amphetamine, alongside with elevated serotonin function. In human studies, Lsamp has been associated with several psychiatric diseases, including schizophrenia, and suicide. Here, we provide a more thorough characterization of the pharmacological phenotype of Lsamp-deficient mice, including testing for sensitivity to morphine, cocaine, MK-801 and ketamine. More thorougly, sensitivity to GABA modulators (diazepam, alprazolam, ethanol, pentobarbital, TP003, and SL651498) was assessed. In brief, Lsamp-deficient mice were more sensitive to the locomotor activating effects of cocaine and morphine, and hypersensitive to the sedative and muscle relaxant effects of GABA modulators, most likely reflecting enhanced function of alpha 1 and alpha 5 subunits of the GABAA receptor. No gross differences in sensitivity to NMDA receptor modulators were observed. Thus, as the lack of Lsamp gene leads to widespread imbalances in major neurotransmitter systems in the brain accompanied by remarkable changes in behavioural phenotype as well, Lsamp-deficient mice are a promising model for mimicking psychiatric disorders.
机译:在与Iglon家族的其他成员组合的细胞粘附分子中的组合中,促进和抑制发育过程中的神经突幼虫和Synapse地层的组合。缺乏LSAMP基因显示的小鼠减少了社会行为,多动症;减少焦虑水平,随着GABAA受体α1和α2亚基的改变平衡;与升高的血清素功能一起降低对安非他明的敏感性。在人类研究中,LSAMP已经与几种精神疾病有关,包括精神分裂症和自杀。在这里,我们提供了Lsamp缺陷小鼠的药理学表型的更全面的表征,包括测试对吗啡,可卡因,MK-801和氯胺酮的敏感性。评估对GABA调节剂(Diazepam,Alprazolam,乙醇,戊巴比妥,TP003和SL651498)的敏感性。简而言之,Lsamp缺陷小鼠对可卡因和吗啡的运动活性效应更敏感,并且对GABA调节剂的镇静剂和肌肉松弛作用的过敏,最可能反映GABAA受体的α1和α5亚基的增强功能。观察到对NMDA受体调节剂的敏感性粗略差异。因此,随着液体缺乏的脑袋缺乏导致大脑中主要神经递质系统中的广泛失衡,同时伴随着行为表型的显着变化,Lsamp缺陷小鼠是模拟精神病疾病的有希望的模型。

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