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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >The role of hippocampal GluR1 and GluR2 receptors in manic-like behavior.
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The role of hippocampal GluR1 and GluR2 receptors in manic-like behavior.

机译：海马GluR1和GluR2受体在躁狂样行为中的作用。

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摘要

The cellular basis underlying the complex clinical symptomatology of bipolar disorder and the mechanisms underlying the actions of its effective treatments have not yet been fully elucidated. This study investigated the role of hippocampal synaptic AMPA receptors. We found that chronic administration of the antimanic agents lithium and valproate (VPA) reduced synaptic AMPA receptor GluR1/2 in hippocampal neurons in vitro and in vivo. Electrophysiological studies confirmed that the AMPA/NMDA ratio was reduced in CA1 regions of hippocampal slices from lithium-treated animals. Reduction in GluR1 phosphorylation at its cAMP-dependent protein kinase A site by the synthetic peptide TAT-S845, which mimics the effects of lithium or VPA, was sufficient to attenuate surface and synaptic GluR1/2 levels in hippocampal neurons in vitro and in vivo. Intrahippocampal infusion studies with the AMPA-specific inhibitor GYKI 52466 [4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine hydrochloride], a GluR1-specific TAT-S845 peptide, showed that GluR1/2 was essential for the development of manic/hedonic-like behaviors such as amphetamine-induced hyperactivity. These studies provide novel insights into the role of hippocampal GluR1/2 receptors in mediating facets of the manic syndrome and offer avenues for the development of novel therapeutics for these disorders.
机译：躁郁症的复杂临床症状的潜在细胞基础及其有效治疗作用的机制尚未完全阐明。这项研究调查了海马突触AMPA受体的作用。我们发现，在体外和体内，长期施用抗躁狂药锂和丙戊酸盐（VPA）可以降低海马神经元中的突触AMPA受体GluR1 / 2。电生理研究证实，锂处理动物海马切片CA1区的AMPA / NMDA比降低。模拟锂或VPA的合成肽TAT-S845降低了其cAMP依赖性蛋白激酶A位点的GluR1磷酸化，足以在体外和体内减弱海马神经元的表面和突触GluR1 / 2水平。用AMPA特异性抑制剂GYKI 52466 [4-（8-甲基-9H-1,3-dioxolo [4,5-h] [2,3]苯并二氮杂-5-基）-盐酸苯甲胺]海马内输注研究GluR1特异性TAT-S845肽表明，GluR1 / 2对于躁狂/享乐主义行为（例如苯丙胺诱导的过度活跃）的发展至关重要。这些研究为海马GluR1 / 2受体在介导躁狂症综合症方面的作用提供了新颖的见解，并为开发针对这些疾病的新型疗法提供了途径。

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