Studies on MDMA and Related Compounds
MDMA 及相关化合物的研究
基本信息
- 批准号:7966892
- 负责人:
- 金额:$ 30.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdolescentAdverse effectsAnimalsArrhythmiaBlood specimenBrainCannulasCathetersCessation of lifeChildClinical ResearchComaCorticosteroneCoupledDopamineDoseDrug usageEmotionalEuropeExhibitsExposure toFeelingFeverHormonesHumanHypertensionHyponatremiaIllicit DrugsImpaired cognitionImplantInjection of therapeutic agentIntakeIntoxicationLiverMediatingMental disordersMicrodialysisNeurosecretory SystemsPaperPharmaceutical PreparationsPharmacology and ToxicologyPlasmaPost-Traumatic Stress DisordersProlactinProsencephalonPublishingRattusReportingResearchRiskSalineSamplingSeizuresSerotoninStudentsSyndromeTemperatureTherapeuticTimeclinically relevantdisturbance in affectecstasyhigh schoolhuman subjectmalemedical complicationmonoamineneurochemistryyoung adult
项目摘要
Two papers were published in this time period. We reported that:
"3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) stimulates the transporter-mediated release of monoamines, including serotonin (5-HT). High-dose exposure to MDMA causes persistent 5-HT deficits (e.g., depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. Male rats received binges of 3 ip injections of MDMA or saline, one injection every 2 h; MDMA was given at a threshold pharmacological dose (1.5 mg/kg 3, low dose) or at a 5-fold higher amount (7.5 mg/kg 3, high dose). One week later, jugular catheters and intracerebral guide cannulae were implanted. Two weeks after binges, rats received acute iv challenge injections of 1 and 3 mg/kg MDMA. Neuroendocrine effects evoked by iv MDMA (prolactin and corticosterone secretion) were assessed via serial blood sampling, while neurochemical effects (5-HT and dopamine release) were assessed via microdialysis in brain. MDMA binges elevated core temperatures only in the high-dose group, with these same rats exhibiting 50% loss of forebrain 5-HT two weeks later. Prior exposure to MDMA did not alter baseline plasma hormones or dialysate monoamines, and effects of iv MDMA were similar in saline and low-dose groups. By contrast, rats pretreated with high-dose MDMA displayed significant reductions in evoked hormone secretion and 5-HT release when challenged with iv MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation."
在此期间发表了两篇论文。我们报道说:
“3,4-亚甲二氧基甲基苯丙胺(MDMA 或摇头丸)会刺激转运蛋白介导的单胺释放,包括血清素 (5-HT)。高剂量暴露于 MDMA 会导致持续的 5-HT 缺乏(例如,大脑 5-HT 耗竭)在动物中,但这种缺陷的功能和临床相关性尚不清楚。在这里,我们研究了 MDMA 诱导的 5-HT 消耗的功能后果。雄性大鼠接受 3 次 ip 注射 MDMA 或生理盐水,每 2 小时注射一次 MDMA,剂量为阈值药理剂量(1.5 mg/kg 3,低剂量)或 5 倍高剂量(7.5 mg)。 /kg 3,高剂量)。一周后,在暴饮暴食两周后,植入颈静脉导管和脑内导管,对大鼠进行急性静脉注射。 3 mg/kg MDMA。通过连续采血评估静脉注射 MDMA 引起的神经内分泌效应(催乳素和皮质酮分泌),同时通过大脑微透析评估神经化学效应(5-HT 和多巴胺释放)。 MDMA 暴饮仅在高剂量组中升高了核心温度,两周后这些大鼠的前脑 5-HT 减少了 50%。先前接触 MDMA 不会改变基线血浆激素或透析液单胺,静脉注射 MDMA 的效果在盐水组和低剂量组中相似。相比之下,用高剂量 MDMA 预处理的大鼠在接受静脉注射 MDMA 攻击时,诱发激素分泌和 5-HT 释放显着减少。由于耐受性仅在暴露于高剂量暴饮暴食的大鼠中产生,因此这种现象涉及高热和 5-HT 耗竭。我们的结果表明,人类对 MDMA 的耐受性可能反映了 5-HT 缺陷,这可能导致剂量进一步增加。”
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Richard Rothman其他文献
Richard Rothman的其他文献
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{{ truncateString('Richard Rothman', 18)}}的其他基金
Medication development of agonist-type treatment agents for stimulant addiction
兴奋剂成瘾激动剂型治疗剂的药物开发
- 批准号:
8336471 - 财政年份:
- 资助金额:
$ 30.06万 - 项目类别:
Development of Dual Dopamine/Serotonin Releasing Agents
双多巴胺/血清素释放剂的开发
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7966890 - 财政年份:
- 资助金额:
$ 30.06万 - 项目类别:
Medication development of non-addicting opioid analgesics
非成瘾阿片类镇痛药的药物开发
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8148551 - 财政年份:
- 资助金额:
$ 30.06万 - 项目类别:
Medication development of non-addicting opioid analgesics
非成瘾阿片类镇痛药的药物开发
- 批准号:
8336473 - 财政年份:
- 资助金额:
$ 30.06万 - 项目类别:
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