Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride)

Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride) (6-OHDA) is an antagonist of the neurotransmitter dopamine^[1]. Oxidopamine hydrochloride is a widely used neurotoxin that selectively destroys dopaminergic neurons^[2]. Oxidopamine hydrochloride is often used to induce animal models of Parkinson's disease (PD)^[3].

In vitro, 24h treatment of PC12 cells with Oxidopamine hydrochloride (0-150µM) induced chromatin condensation in a concentration- and time-dependent manner, increased the activity of caspase-3, -8, and -9 in cells, and depolarized the mitochondrial membrane^[4]. 24h treatment of Neuro-2a and SH-SY5Y cells with Oxidopamine hydrochloride (0-500µM) reduced the viability of both cells in a concentration-dependent manner, with similar EC₅₀ values​(approximately 110µM), and induced cyclooxygenase-2 (COX-2) expression and nuclear translocation^[5].

In vivo, Oxidopamine hydrochloride (8μg in 2μL saline) was injected into the medial forebrain bundle in old and young rats, which showed significant impairment in the contralateral forelimb reaching test and forced choice task, and a significant decrease in TH-expressing cells in the substantia nigra pars compacta (SNpc) and striatum^[6]. Oxidopamine hydrochloride (5μg in 2μL saline) was injected unilaterally into the right striatum in SD rats, which induced nigrostriatal nerve terminal lesions, reduced striatal dopamine levels, and reduced the number of tyrosine hydroxylase immunoreactive cells in the ipsilateral substantia nigra, accompanied by significant atrophy of the remaining dopaminergic neurons^[7].

References:
[1] De Boer P, Damsma G, Schram Q, et al. The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis: the importance of the post-surgery interval[J]. Naunyn-Schmiedeberg's archives of pharmacology, 1992, 345: 144-152.
[2] Pantic I, Cumic J, Skodric S R, et al. Oxidopamine and oxidative stress: Recent advances in experimental physiology and pharmacology[J]. Chemico-biological interactions, 2021, 336: 109380.
[3] Torres E M, Dunnett S B. 6-OHDA lesion models of Parkinson’s disease in the rat[J]. Animal Models of Movement Disorders: Volume I, 2012: 267-279.
[4] Fujita H, Ogino T, Kobuchi H, et al. Cell-permeable cAMP analog suppresses 6-hydroxydopamine-induced apoptosis in PC12 cells through the activation of the Akt pathway[J]. Brain research, 2006, 1113(1): 10-23.
[5] Kang X, Qiu J, Li Q, et al. Cyclooxygenase-2 contributes to oxidopamine-mediated neuronal inflammation and injury via the prostaglandin E2 receptor EP2 subtype[J]. Scientific reports, 2017, 7(1): 9459.
[6] Barata-Antunes S, Teixeira F G, Mendes-Pinheiro B, et al. Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease[J]. International journal of molecular sciences, 2020, 21(10): 3459.
[7] Jin F, Wu Q, Lu Y F, et al. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats[J]. European journal of pharmacology, 2008, 600(1-3): 78-82.

Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride)（6-OHDA）是神经递质多巴胺的拮抗剂^[1]。Oxidopamine hydrochloride是一种广泛应用的神经毒素，可选择性破坏多巴胺能神经元^[2]。Oxidopamine hydrochloride常用于诱导帕金森病（PD）动物模型^[3]。

在体外，Oxidopamine hydrochloride（0-150µM）处理PC12细胞24h，以浓度和时间依赖的方式诱导了细胞染色质凝聚，增加了细胞中caspase-3、-8和-9的活性，使线粒体膜去极化^[4]。Oxidopamine hydrochloride（0-500µM）处理Neuro-2a和SH-SY5Y细胞24h，以浓度依赖的方式降低了两种细胞的活力，具有相似的EC₅₀值（约110µM），诱导环氧合酶-2（COX-2）表达和核转位^[5]。

在体内，Oxidopamine hydrochloride（8μg in 2μL saline）通过注射至内侧前脑束处理老年和年轻大鼠，在对侧前肢伸手测试和强制选择任务中均表现出明显障碍，并且黑质致密部（SNpc）和纹状体中TH表达细胞明显减少^[6]。Oxidopamine hydrochloride（5μg in 2μL saline）通过单侧注入右侧纹状体处理SD大鼠，诱导了黑质纹状体神经末梢病变，降低了纹状体多巴胺水平，减少了同侧黑质中酪氨酸羟化酶免疫反应性细胞数量，并伴有剩余多巴胺能神经元的显著萎缩^[7]。