Mephedrone alters basal ganglia and limbic neurotensin systems.
Mephedrone alters basal ganglia and limbic neurotensin systems.
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DOI：
10.1111/jnc.12727
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发表时间：
2014-08
影响因子：
4.7
通讯作者：
Hanson GR
中科院分区：
文献类型：
--
作者：
German CL;Hoonakker AH;Fleckenstein AE;Hanson GR
甲氧麻黄酮（4-甲基卡西酮）是一种合成的卡西酮设计药物，它像许多精神兴奋剂一样改变突触前多巴胺（DA）的活性。然而，对甲氧麻黄酮突触后多巴胺能的影响知之甚少。神经肽神经紧张素（NT）对基底节区和边缘区DA通路提供抑制反馈，突触后d1样和d2样受体活性影响NT组织水平。本研究评估了甲氧麻黄酮如何改变基底神经节和边缘系统NT含量以及NT受体激活在药物消费行为中的作用。4次注射25 mg/kg的甲氧麻黄酮可增加基底节区（纹状体、黑质和苍白球）和边缘区（伏隔核核心）NT含量，而低剂量（5 mg/kg/注射）仅增加纹状体NT含量。甲菲酮诱导的基底神经节NT水平升高是由纹状体d1样受体介导的，而黑质则是由苍白球d1样受体和d2样受体介导的。甲氧麻黄酮增加了苍白球中另一种神经肽P物质的含量，但在背纹状体和黑质中没有增加。最后，NT受体激动剂PD149163阻断甲氧麻黄酮的自我给药，表明NT释放减少，如组织水平增加所示，可能有助于甲氧麻黄酮的消耗模式。
Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters presynaptic dopamine (DA) activity like many psychostimulants. However, little is known about the postsynaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and postsynaptic D1-like and D2-like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1-like receptors in the striatum and the substantia nigra by both D1-like and D2-like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.
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影响因子：
6.1
作者：
German, Christopher L.;Fleckenstein, Annette E.;Hanson, Glen R.
通讯作者：
Hanson, Glen R.
影响因子：
5
作者：
CASTEL, MN;MORINO, P;HOKFELT, T
通讯作者：
HOKFELT, T
影响因子：
3.4
作者：
Alburges, Mario E.;Frankel, Paul S.;Hanson, Glen R.
通讯作者：
Hanson, Glen R.
影响因子：
3.3
作者：
Hanson, G. R.;Hoonakker, A. J.;Alburges, M. E.;McFadden, L. M.;Robson, C. M.;Frankel, P. S.
通讯作者：
Frankel, P. S.
DOI：
10.1124/jpet.111.184119
发表时间：
2011-11-01
影响因子：
3.5
作者：
Hadlock, Gregory C.;Webb, Katy M.;Fleckenstein, Annette E.
通讯作者：
Fleckenstein, Annette E.