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大剂量(+)-甲基苯丙胺、5-甲氧基二异丙基色胺和(±)-3,4-亚甲基二氧甲基苯丙胺对大鼠的脑电图及惊厥作用

Electroencephalographic and convulsive effects of binge doses of (+)-methamphetamine, 5-methoxydiisopropyltryptamine, and (±)-3,4-methylenedioxymethamphetamine in rats.

作者信息

Graham Devon L, Herring Nicole R, Schaefer Tori L, Holland Katherine D, Vorhees Charles V, Williams Michael T

机构信息

Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH ; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

出版信息

Open Neuropsychopharmacol J. 2012;5:1-8. doi: 10.2174/1876523801205010001.

Abstract

The abuse of drugs such as methamphetamine (MA), 3,4-methylenedioxymethamphetamine (Ecstasy, MDMA), and 5-methoxydiisopropyltryptamine (5-MeO-DIPT; Foxy) is global. Symptoms from taking these drugs include tachycardia, agitation, hyperpyrexia, and sometimes seizures. We compared the EEG effects of these drugs in male Sprague-Dawley rats (~300 g) implanted with cortical electroencephalographic (EEG) electrodes prior to testing. Animals received four subcutaneous injections of MA, MDMA, or Foxy (10 mg/kg each as freebase, administered every 2 h), or saline as these doses produce lasting effects on learning, memory, and monoamines. EEG tracings were recorded before, during, and after treatment. Animals receiving MDMA showed no significant EEG abnormalities or myoclonus. MA treatment resulted in myoclonic activity and in brief (<10 s) EEG epileptiform activity in ~50% of the rats. Longer seizure activity (10 s to 5 min) was recorded in some MA-treated rats following the third and fourth doses. The onset of myoclonic activity following Foxy treatment occurred shortly after the first dose. All rats receiving Foxy showed seizures by the second dose and this continued throughout the treatment regimen. The results show that binge doses of MA and MDMA, which mimic the neurochemical changes seen in chronic users, increase EEG abnormalities after MA but not after MDMA. While the neurochemical effects of Foxy are not known in humans, this drug causes severe EEG abnormalities and overt seizures in 100% of tested animals.

摘要

甲基苯丙胺(MA)、3,4-亚甲基二氧甲基苯丙胺(摇头丸,MDMA)和5-甲氧基二异丙基色胺(5-MeO-DIPT;狐仙)等药物的滥用现象在全球范围内都存在。服用这些药物的症状包括心动过速、激动、高热,有时还会出现癫痫发作。我们比较了这些药物对雄性Sprague-Dawley大鼠(约300克)的脑电图(EEG)影响,这些大鼠在测试前已植入皮质脑电图电极。动物接受了四次皮下注射MA、MDMA或狐仙(每种药物以游离碱形式10毫克/千克,每2小时注射一次),或注射生理盐水,因为这些剂量会对学习、记忆和单胺产生持久影响。在治疗前、治疗期间和治疗后记录脑电图描记图。接受MDMA的动物未出现明显的脑电图异常或肌阵挛。MA治疗导致约50%的大鼠出现肌阵挛活动和短暂(<10秒)的脑电图癫痫样活动。在第三次和第四次给药后,一些接受MA治疗的大鼠记录到了更长时间的癫痫活动(10秒至5分钟)。狐仙治疗后肌阵挛活动在第一剂后不久就开始出现。所有接受狐仙治疗的大鼠在第二剂时都出现了癫痫发作,并且在整个治疗过程中持续发作。结果表明,模仿慢性使用者神经化学变化的大剂量MA和MDMA,在MA给药后会增加脑电图异常,但MDMA给药后不会。虽然狐仙对人类的神经化学影响尚不清楚,但这种药物在100%的受试动物中会导致严重的脑电图异常和明显的癫痫发作。

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