DOPAMINE RELEASE INDUCED BY 4-METHYLAMINOREX

新的兴奋剂药物4-甲氨基酚(4-Max；2-氨基-4-甲基-5- 苯并恶唑啉；街名U4Eeh最近作为一种 滥用毒品。吸毒者描述了4种药物的主观影响- 麦克斯就像安非他命和可卡因一样，而4-麦克斯就是自我 猴子以类似于可卡因的方式给药。事实上，在 秘密市场，4-Max经常被毒贩歪曲为 可卡因或安非他明。非法制造的4-Max已经被 被佛罗里达州、加利福尼亚州和宾夕法尼亚州当局没收。到期 由于这种物质被滥用的可能性很大，所以顺式异构体4- Max被分配到受控者的附表1药物类别 1987年10月颁布的《物质法》。当局担心， 该化合物的合成和前体的可获得性将导致 更广泛地滥用4-Max。尽管如此，人们对此知之甚少。 关于它对中枢神经系统的药理作用。这个 有限的数据表明，4-Max具有刺激性、厌食性和 拟交感神经的特性类似于特征良好的 兴奋剂安非他明。安非他命主要通过它的 对大脑多巴胺和去甲肾上腺素系统的作用。稀缺的现存 4-Max上提供的生化和行为数据也一致 假设4-Max通过与 大脑中的多巴胺系统。4 MAX以四种不同的异构体形式存在 在效力上。这项建议的总体目标是检查 我们的4-MAX的异构体诱导释放 脑内部分前脑结构的神经递质多巴胺 唤醒自由活动的老鼠。样本将通过微透析法收集 技术，样品中的多巴胺含量将被定量 采用高效液相色谱(HPLC)进行分析。中脑 腹侧被盖区(A10)的多巴胺神经元 多巴胺神经元的生化和生理特性 发现于邻近的黑质区(A9)。因此，多巴胺 释放将在几个不同的前脑区域进行检查，这些区域是 选择性地只被这两种多巴胺中的一种支配 神经元。这一点很重要，因为与苯丙胺不同，初步数据 表明4-MAX对电磁场有不同的影响 这两组多巴胺神经元的放电活动。在……里面 刺激性行为的选择性实验观察 变化将与同时测量的多巴胺相关。 放手。此外，4-MAX诱导释放的机制 多巴胺的含量将会被检测。在所有拟议的研究中， 4-Max的效果将与原型的效果进行比较 兴奋剂安非他明。我们的方法应该会产生关于 4-MAX异构体对大鼠脑内含多巴胺神经元的作用 这将有助于我们理解4-Max的作用模式。

The novel stimulant drug 4-methylaminorex (4-MAX;2-amino-4-methyl-5- phenyloxazoline; street name "U4Euh" has recently gained attention as a drug of abuse. Drug users have described the subjective effects of 4- MAX to be like those of amphetamine and cocaine, and 4-MAX is self- administered by monkeys in a manner similar to cocaine. IN fact, on the clandestine market, 4-MAX is often misrepresented by drug dealers as cocaine or amphetamine. Illegally manufactured 4-MAX has been confiscated by authorities in Florida, California and pennsylvania. Due to the high potential for abuse of this substance, the cis isomer of 4- MAX was assigned to the schedule 1 drug category of the Controlled Substances Act in October, 1987. Authorities fear that the ease of synthesis of this compound and the accessibility of precursors will lead to more widespread abuse of 4-MAX. Nonetheless, very little is known about its pharmacological actions on the central nervous system. The limited data available suggest that 4-MAX has stimulant, anorectic and sympathomimetic properties similar to those of the well characterized stimulant amphetamine. Amphetamine primarily exerts its effects via its action on brain dopamine and norepinephrine systems. The scant existing biochemical and behavioral data available on 4-MAX are also consistent with the hypothesis that 4-MAX produces its effects by interacting with brain dopamine systems. 4 Max exists in four isomeric forms which vary in potency. The overall goal of this proposal is to examine the ability of the our isomers of 4-MAX to induce the release of the neurotransmitter dopamine from selected forebrain structures in the awake freely moving rat. The samples will be collected by microdialysis technique, and dopamine content in the samples will be quantitatively analyzed by high performance liquid chromatography (HPLC). Midbrain dopamine neurons in the ventral tegmental area (A10) have different biochemical and physiological characteristics than dopamine neurons found in the adjacent substantia nigra region (A9). Hence, dopamine release will be examined in several different forebrain areas which are selectively innervated by only one of these two populations of dopamine neurons. This is important since, unlike amphetamine, preliminary data indicate that 4-MAX has a differential effect on the electrical discharge activity of these two populations of dopamine neurons. In selected experiments observations of stimulant-induced behavioral changes will be correlated with simultaneous measures of dopamine release. In addition, the mechanism by which 4-MAX induces the release of dopamine will be examined. In all of the proposed studies the effects of 4-MAX will be compared to the effects of the prototypical stimulant amphetamine. Our approach should yield important data about the action of the isomers of 4-MAX on dopamine-containing neurons in the brain, which will help us to understand the mode of action of 4-MAX.