NEUROCHEMICAL ALTERATIONS BY DESIGNER DRUGS

滥用3，4-亚甲基二氧基甲基苯丙胺(MDMA)或摇头丸， 继续增加，特别是在大学校园。在.期间 在之前的资助期间，我们和其他人已经研究过神经化学物质 在一次大剂量或重复较小剂量的 摇头丸。色氨酸羟化酶(TPH)活性显著降低， 5-羟色胺及其代谢物5-羟基吲哚乙酸 (5HIAA)，已经在几个大脑区域观察到；这些变化在 5-羟色胺能参数持续很长一段时间 停用这种药物。 在目前的提案中，千年发展目标和其 同系物造成的影响将被调查。可能扮演的角色 兴奋性氨基酸在MDMA中的诱导作用 下定决心。多巴胺(DA)和/或GHT是否参与MDMA- 诱导效应将通过以前在 我们对甲基苯丙胺及其类似物的调查；在 这项研究我们将确定MDMA诱导的大脑变化 神经肽浓度。氧化应激的重要性和 将探讨肾上腺类固醇在反应中的可能作用。这个 还将研究对MDMA及其同系物的耐受性的发展。 最后，4-甲氨基酚(尿素)的神经化学效应，一种类似物 最近出现在街上的，将被调查。 这些研究不仅将提供有关神经化学物质的信息 滥用MDMA和类似的特制药物的影响，但 多巴胺能、5-羟色胺能和神经递质的相互关系 神经肽系统也将被研究。

The abuse of 3,4-methylenedioxymethamphetamine (MDMA), or ecstasy, continues to increase, especially on college campuses. During the previous grant period we an others have investigated the neurochemical alterations that occur after one large or repeated smaller doses of MDMA. Profound decreases in tryptophan hydroxylase (TPH) activity and in 5-hydroxytryptamine (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA), have been observed in several brain regions; these changes in serotonergic parameters persist for long periods of time after discontinuning the drug. In the current proposal, the mechanisms(s) by which MDMA and its congeners cause their effects will be investigated. The possible role of excitatory amino acids in the MDMA-induced effects will be determined. Whether dopamine (DA) and/or GHT are involved in the MDMA- induced effects will be assessed by techniques previously employed in our investigation of methamphetamine and its analogs; in this part of the study we will determine the MDMA-induced changes in brain neuropeptide concentrations. The importance of oxidative stress and the possible role of adrenal steroids in the response will be explored. The development of tolerance to MDMA and its congeners will also be studied. Finally, the neurochemical effects of 4-methylaminorex (UrEA), an analog that has recently appeared on the street, will be investigated. Not only will these studies provide information on the neurochemical effects of abuse of MDMA and similar designer drugs, but the interrelationship between the dopaminergic, serotonergic and neuropeptide systems will also be investigated.