首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity
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Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity

机译:在大鼠发育乙醇暴露后的行为缺陷和细胞损伤通过CP-101,606,NMDAR拮抗剂具有独特的NR2B特异性

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摘要

NMDAR-mediated excitotoxicity has been implicated in some of the impairments following fetal ethanol exposure. Previous studies suggest that both neuronal cell death and some of the behavioral deficits can be reduced by NMDAR antagonism during withdrawal, including antagonism of a subpopulation of receptors containing NR2B subunits. To further investigate NR2B involvement, we selected a compound, CP-101,606 (CP) which binds selectively to NR2B/2B stoichiometries, for both in vitro and in vivo analyses. For the in vitro study, hippocampal explants were exposed to ethanol for 10 days and then 24 h following removal of ethanol, cellular damage was quantified via propidium iodide fluorescence. In vitro ethanol withdrawal-associated neurotoxicity was prevented by CP (10 and 25 nM). In vivo ethanol exposure was administered on PNDs 1-7 with CP administered 21 h following cessation. Activity (PNDs 20-21), motor skills (PNDs 31-33), and maze navigation (PNDs 43-44) were all susceptible to ethanol insu treatment with CP (15 mg/kg) rescued these deficits. Our findings show that CP-101,606, a drug that blocks the NR2B/2B receptor, can reduce some of the damaging effects of "3rd trimester" alcohol exposure in our rodent model. Further work is clearly warranted on the neuroprotective potential of this drug in the developing brain.
机译:鼻腔介导的兴奋毒性涉及胎儿乙醇暴露后的一些损伤。先前的研究表明,在戒断期间NMDAR拮抗作用可以减少神经元细胞死亡和一些行为缺陷,包括含有NR2B亚基的受体亚群的拮抗作用。为了进一步研究NR2B的参与,我们选择了一种化合物,CP-101,606(CP),其在体外和体内分析中选择性地与NR2B / 2B化学物质中选择性结合。对于体外研究,海马外植体暴露于乙醇10天,然后在除去乙醇后24小时,通过碘化丙锭量化细胞损伤。通过CP(10和25nm)防止体外乙醇戒断相关的神经毒性。在Vivo乙醇暴露中,在停止后21小时施用CP,施用PNDs 1-7。活动(PNDS 20-21),电机技能(PNDS 31-33)和迷宫导航(PNDS 43-44)都易于乙醇侮辱;用CP(15 mg / kg)治疗救出了这些赤字。我们的研究结果表明,CP-101,606,阻断NR2B / 2B受体的药物,可以减少啮齿动物模型中的“3rd三三个月”酒精暴露的一些破坏性效果。进一步的工作明显保证了这种药物在发育中的大脑中的神经保护潜力。

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