Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum.
Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum.
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DOI：
10.1111/j.1471-4159.2011.07632.x
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Kuhn DM
中科院分区：
文献类型：
--
作者：
Angoa-Pérez M;Kane MJ;Francescutti DM;Sykes KE;Shah MM;Mohammed AM;Thomas DM;Kuhn DM
甲基苯丙胺酮（4-甲基甲卡西酮）是一种β-酮基苯丙胺，与取代苯丙胺和卡西酮衍生物具有密切的结构相似性。近年来，甲氧麻黄酮的滥用急剧增加，已成为美国和欧洲的一个重大公共卫生问题。遗憾的是，关于4-甲基甲卡西酮的药理学和神经化学作用的资料很少。鉴于4-甲基甲卡西酮已被证明有滥用的可能性，并考虑到其与甲基苯丙胺和甲卡西酮的相似性，了解4-甲基甲卡西酮是否与这些药剂一样具有对纹状体多巴胺神经末梢造成损害的能力尤为重要。因此，我们用甲氧麻黄酮（4 × 20或40 mg/kg）的暴食样方案治疗小鼠，并在治疗后2或7天检查纹状体的神经毒性证据。虽然甲氧麻黄酮引起体温过高和运动刺激，但在目前使用的任何治疗条件下，它都不会降低多巴胺、酪氨酸羟化酶或多巴胺转运蛋白的纹状体水平。此外，甲氧麻黄酮不会引起纹状体中的小胶质细胞活化，也不会增加胶质细胞酸性蛋白水平。总之，这些令人惊讶的结果表明，甲氧麻黄酮，尽管其与甲基苯丙胺和卡西酮衍生物的许多机制重叠，不引起纹状体的多巴胺神经末梢的神经毒性。
Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the US and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4X 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum.
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影响因子：
5.8
作者：
KALIX, P;GLENNON, RA
通讯作者：
GLENNON, RA
影响因子：
5.3
作者：
LaVoie, MJ;Card, JP;Hastings, TG
通讯作者：
Hastings, TG
影响因子：
2.7
作者：
Banjaw, MY;Schmidt, WJ
通讯作者：
Schmidt, WJ
影响因子：
4.2
作者：
KUHN, DM;BILLINGSLEY, ML
通讯作者：
BILLINGSLEY, ML
影响因子：
7.3
作者：
Kehr, J.;Ichinose, F.;Yoshitake, T.
通讯作者：
Yoshitake, T.