Evidence for involvement of nitric oxide and GABA(B) receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex.
Evidence for involvement of nitric oxide and GABA(B) receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex.
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DOI：
10.1016/j.neuropharm.2012.04.032
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发表时间：
2012-09
影响因子：
4.7
通讯作者：
Richtand NM
中科院分区：
文献类型：
--
作者：
Roenker NL;Gudelsky GA;Ahlbrand R;Horn PS;Richtand NM
NMDA受体拮抗剂的全身给药提高了前额叶皮层内的细胞外谷氨酸。NMDA受体阻断的认知和行为效应与精神分裂症的症状直接相关，最近的研究表明一氧化氮和GABAB受体在介导NMDA受体阻断对这些行为的影响中起重要作用。我们试图通过直接测量一氧化氮和GABAB受体机制对MK-801诱导的前额叶皮层谷氨酸释放的影响来扩展这些观察结果。通过微透析法测定，雄性Sprague-Dawley大鼠全身注射MK-801（0.3 mg/kg）显著增加了前额叶皮层细胞外谷氨酸水平。这种作用可被一氧化氮合酶抑制剂L-NAME（60 mg/kg）阻断。将一氧化氮供体SNAP（0.5 - 5 mM）直接反向透析至前额叶皮质模拟全身MK-801的作用，剂量依赖性地升高皮质细胞外谷氨酸。MK-801的作用也可通过GABAB受体激动剂巴氯芬（5 mg/kg）全身给药阻断。总之，这些数据表明，增加一氧化氮的形成是必要的NMDA拮抗剂诱导的前额叶皮层细胞外谷氨酸的升高。此外，数据表明GABAB受体激活可以调节NMDA拮抗剂诱导的皮质谷氨酸释放增加。
Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release.
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DOI：
10.1111/j.1742-7843.2004.pto940203.x
发表时间：
2004-02-01
影响因子：
3.1
作者：
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通讯作者：
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发表时间：
2009-05-01
影响因子：
4.8
作者：
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影响因子：
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