一氧化氮合酶抑制剂对苯丙胺神经毒性引发的大脑中乙酰胆碱释放及一氧化氮水平变化的影响。

Influence of NOS inhibitors on changes in ACH release and NO level in the brain elicited by amphetamine neurotoxicity.

作者信息

Bashkatova V, Kraus M, Prast H, Vanin A, Rayevsky K, Philippu A

机构信息

Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.

出版信息

Neuroreport. 1999 Oct 19;10(15):3155-8. doi: 10.1097/00001756-199910190-00006.

DOI:10.1097/00001756-199910190-00006

PMID:10574552

Abstract

We studied the possible role of neurotoxicity in the d,l-amphetamine (AMPH)-induced release of acetylcholine (ACH) in the nucleus accumbens (Nac) and the involvement of endogenous NO in this process. For determination of ACH release the Nac was superfused using the push-pull-technique. NO was directly measured using the electron paramagnetic resonance technique. Repeated administration of AMPH increased ACH release by about 400%. N-nitro-L-arginine (L-NNA) and 7-nitroindazole (7-NI) nearly abolished the AMPH-induced increase in ACH release. AMPH increased NO as well as lipid peroxidation (LPO) products in the cortex. L-NNA and 7-NI substantially diminished NO increase. AMPH-evoked LPO was only slightly reduced by these compounds. It is concluded that AMPH enhances ACH release through increased NO synthesis and induces neurotoxicity via NO and by LPO independent NO generation.

摘要

我们研究了神经毒性在d，l-苯丙胺（AMPH）诱导的伏隔核（Nac）中乙酰胆碱（ACH）释放中的可能作用，以及内源性一氧化氮（NO）在此过程中的参与情况。为了测定ACH释放，采用推挽技术对Nac进行灌流。使用电子顺磁共振技术直接测量NO。重复给予AMPH可使ACH释放增加约400%。N-硝基-L-精氨酸（L-NNA）和7-硝基吲唑（7-NI）几乎完全消除了AMPH诱导的ACH释放增加。AMPH增加了皮质中的NO以及脂质过氧化（LPO）产物。L-NNA和7-NI显著减少了NO的增加。这些化合物仅略微降低了AMPH诱发的LPO。结论是，AMPH通过增加NO合成增强ACH释放，并通过NO以及不依赖NO的LPO生成诱导神经毒性。