Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice.
Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice.
复制标题
眶额皮质在小鼠 NMDA 受体阻断诱导的过度运动中发挥着重要作用。
DOI：
10.1016/j.bbrc.2016.10.089
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Hashimoto H.
中科院分区：
文献类型：
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作者：
Seiriki K;Kasai A;Kuwaki T;Nakazawa T;Yamaguchi S;Hashimoto H.
谷氨酰胺-甲基-d-天冬氨酸（NMDA）受体在多种神经和精神疾病中发挥重要作用。非竞争性NMDA受体拮抗剂阻断导致拟精神效应；然而，负责这种影响的大脑区域还没有被很好地理解。在这里，我们利用Arc::dVenus报告小鼠，通过将Arc表达作为神经元活动的指标，确定了对MK-801（一种非竞争性NMDA受体拮抗剂）有反应的特定脑区。MK-801主要在眼窝前额皮质（OFC）增加了金星的表达，正如预期的那样，诱导了明显的过度运动。局部OFC病变选择性地减弱mk -801诱导的早期（0-30分钟）过度运动。此外，氯氮平，一种非典型抗精神病药，有效地减弱了mk -801诱导的OFC和过度运动中的dVenus表达。这些结果表明OFC可能在NMDA受体介导的精神样行为异常中起关键作用。
GlutamatergicN-methyl-d-aspartate (NMDA) receptors play critical roles in several neurological and psychiatric diseases. Blockade by noncompetitive NMDA receptor antagonist leads to psychotomimetic effects; however, the brain regions responsible for the effects are not well understood. Here, we determined the specific brain regions responsive to MK-801, a noncompetitive NMDA receptor antagonist, by mappingArcexpression as an indicator of neuronal activity using Arc::dVenus reporter mice. MK-801 increased dVenus expression predominantly in the orbitofrontal cortex (OFC) and, as expected, induced a marked hyperlocomotion. Local OFC lesions selectively attenuated the early phase (0–30 min) of MK-801-induced hyperlocomotion. Further, clozapine, an atypical antipsychotic, effectively attenuated both the MK-801-induced dVenus expression in the OFC and hyperlocomotion. These results suggest that the OFC may be critically involved in NMDA receptor-mediated psychotic-like behavioral abnormalities.