Characterization of electroencephalographic and biochemical responses at 5-HT promoting drug-induced onset of serotonin syndrome in rats.

Characterization of electroencephalographic and biochemical responses at 5-HT promoting drug-induced onset of serotonin syndrome in rats.
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DOI:
10.1111/jnc.12141
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发表时间:
2013-06
影响因子:
4.7
通讯作者:
Tao R
Tao R
中科院分区:
医学2区
文献类型:
--
作者:
Ma Z;Rudacille M;Prentice HM;Tao R

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许多用于药物治疗或非法娱乐目的的精神药物能够增加CNS中的细胞外5-羟色胺(5-HT)。众所周知,5 HT可以改善情绪,但只有当其释放水平在适当范围内时。过量的5 HT是有害的,通常会导致血清素综合征。迄今为止,由于缺乏可用的实验室测试,5-羟色胺综合征的临床诊断完全依赖于症状的观察。本研究的目的是使用实验室设置来表征综合征的发作,以确定过度的5 HT诱发的神经系统异常。用三组促5-HT药物(1)(±)-3,4-亚甲二氧基甲基苯丙胺(MDMA)、单胺氧化酶抑制剂氯吉兰与5-HT前体5-羟色氨酸的联合作用、氯吉兰与选择性重摄取抑制剂帕罗西汀的联合作用,诱发大鼠的上述综合征。该综合征的发病特征是脑电图(EEG),震颤和脑/血浆5-HT试验。我们发现,轻度综合征与脑电图振幅降低有关,而重度综合征则与癫痫样脑电图活动和震颤活动增加密切相关。微透析证实了该综合征的发生,显示脑透析液中过量的5 HT流出和血浆中未结合的5 HT浓度增加。我们的研究结果表明,综合征的发病可以揭示脑电图记录,震颤活动和血浆中未结合的5-HT浓度的变化。
Many psychotropic substances used either for medications or illicit recreational purposes are able to produce an increase in extracellular serotonin (5HT) in the CNS. 5HT is well known to improve mood, however, only when the levels of its release are in an appropriate range. Excessive 5HT is harmful, and will generally result in serotonin syndrome. To date, clinical diagnosis of serotonin syndrome relies exclusively on observation of symptoms because of a lack of available laboratory tests. The goal of the present study was to characterize the onset of the syndrome using laboratory settings to determine excessive 5HT-evoked neurological abnormalities. Experiments were carried out in rats with the syndrome being elicited by three groups of 5HT-promoting drugs: 1) (±)-3,4-methylenedioxymethamphetamine (MDMA); 2) a combination of the monoamine oxidase inhibitor clorgyline with the 5HT precursor 5-hydroxytryptophan; 3) clorgyline combined with the serotonin-selective reuptake inhibitor paroxetine. The onset of the syndrome was characterized by electroencephalography (EEG), tremor and brain/plasma 5HT tests. We found that a mild syndrome was associated with reduced EEG amplitudes while a severe syndrome strongly with seizure-like EEG activity and increased tremor activity. The occurrence of the syndrome was confirmed with microdialysis, showing excessive 5HT efflux in brain dialysate and the increased concentration of unbound 5HT in the plasma. Our findings suggest that the syndrome onset can be revealed with EEG recording, measurements of tremor activity and changes of unbound 5HT concentration in the plasma.
DOI: 10.1111/j.1600-0447.2011.01706.x
发表时间: 2011-12-01
影响因子: 6.7
作者:
Parker, G.;Brotchie, H.
通讯作者: Brotchie, H.
DOI: 10.1007/bf00444703
发表时间: 1989-01-01
期刊: PSYCHOPHARMACOLOGY
影响因子: 3.4
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FLETCHER, PJ;YU, PH
通讯作者: YU, PH
DOI: 10.1097/00063110-200312000-00013
发表时间: 2003-12-01
影响因子: 4.4
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Ben-Abraham, Ron;Szold, Oded;Weinbroum, Avi A.
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DOI: 10.1016/0013-4694(72)90177-0
发表时间: 1972-01-01
期刊: ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子: --
作者:
RACINE, RJ
通讯作者: RACINE, RJ
DOI: 10.1080/15563650802304401
发表时间: 2008-12-01
影响因子: 3.3
作者:
George, Mathew;Al-Duaij, Nadeem;Shannon, Michael Wayne
通讯作者: Shannon, Michael Wayne