MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.
MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.
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DOI：
10.1007/s11481-012-9420-x
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发表时间：
2013-03
影响因子：
6.2
通讯作者：
Gudelsky, Gary A.
中科院分区：
文献类型：
--
作者：
Anneken, John H.;Cunningham, Jacobi I.;Collins, Stuart A.;Yamamoto, Bryan K.;Gudelsky, Gary A.
3，4-亚甲二氧基甲基苯丙胺（MDMA;摇头丸）是一种流行的滥用药物，对多巴胺能、多巴胺能和胆碱能递质系统有充分记录的急性作用，并有证据表明对大鼠大脑中的多巴胺能系统有长期破坏作用。最近，研究表明，MDMA引起海马中谷氨酸释放的延迟和持续增加。本研究的目的是确定炎症介质在MDMA诱导的谷氨酸释放增加中的作用，以及炎症途径在与重复MDMA治疗相关的持续神经化学毒性中的作用。用非选择性环氧合酶（考克斯）抑制剂酮洛芬和考克斯-2选择性抑制剂尼美舒利处理减弱了由重复MDMA暴露（10 mg/kg，i. p.，每2小时一次）;在用考克斯-1选择性抑制剂吡罗昔康处理的大鼠中没有观察到衰减。考克斯活性的主要产物前列腺素E2的反向透析也导致海马中细胞外谷氨酸的显著增加。重复暴露于MDMA减少了海马齿状回中小清蛋白阳性GABA中间神经元的数量，酮洛芬治疗减弱了这种作用。然而，用酮洛芬抑制考克斯并不能阻止由MDMA处理引起的海马中5-HT的长期消耗。这些数据支持这样的观点，即环氧合酶活性有助于增加谷氨酸释放和减少GABA中间神经元在大鼠海马中产生的重复MDMA暴露的机制。
3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus. Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.
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影响因子：
4.7
作者：
Anneken JH;Gudelsky GA
通讯作者：
Gudelsky GA
影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
3.4
作者：
Burgess, Adrian P.;Venables, Louise;Parrott, Andrew C.
通讯作者：
Parrott, Andrew C.
影响因子：
4.2
作者：
Meller, R;Harrison, PJ;Sharp, T
通讯作者：
Sharp, T
影响因子：
3.4
作者：
Armstrong, BD;Noguchi, KK
通讯作者：
Noguchi, KK