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大豆黄酮调节 CD-1 雄性小鼠可卡因强化效应和线索诱导的可卡因复吸。

Daidzein modulates cocaine-reinforcing effects and cue-induced cocaine reinstatement in CD-1 male mice.

机构信息

Integrative Pharmacology and Systems Neuroscience Research Group, Hospital del Mar Medical Research Institute (IMIM), Parc de Recerca Biomedica de Barcelona (PRBB), C/Dr. Aiguader 88, 08003, Barcelona, Spain.

Laboratory of Neuropharmacology, Parc de Recerca Biomedica de Barcelona (PRBB), Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003, Barcelona, Spain.

出版信息

Psychopharmacology (Berl). 2021 Jul;238(7):1923-1936. doi: 10.1007/s00213-021-05820-z. Epub 2021 Apr 11.

DOI:10.1007/s00213-021-05820-z
PMID:33839903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8233246/
Abstract

RATIONALE

Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables like soybeans that share a common chemical structure. Previous studies have described that synthetic derivatives from the natural isoflavone daidzin can modulate cocaine addiction, by a mechanism suggested to involve aldehyde-dehydrogenase (ALDH) activities.

OBJECTIVES

Based on these previous studies, we investigated the effects of three natural isoflavones, daidzin, daidzein, and genistein, on the modulation of the cocaine reinforcing effects and on cue-induced reinstatement in an operant mouse model of cocaine self-administration.

RESULTS

Chronic treatment with daidzein or genistein decreased operant responding to obtain cocaine intravenous infusions. On the other hand, daidzein and daidzin, but not genistein, were effective in decreasing cue-induced cocaine reinstatement. Complementary studies revealed that daidzein effects on cocaine reinforcement were mediated through a mechanism that involved dopamine type-2/3 receptors (DA-D2/3) activities.

CONCLUSIONS

Our results suggest that these natural compounds alone or in combination can be a potential therapeutic approach for cocaine addiction. Further clinical studies are required in order to ascertain their potential therapeutic use.

摘要

原理

可卡因成瘾是一种慢性复发性疾病，缺乏有效的治疗方法。异黄酮是一类存在于不同植物和蔬菜（如大豆）中的化合物，它们具有共同的化学结构。先前的研究表明，天然异黄酮染料木黄酮的合成衍生物可以通过一种被认为涉及醛脱氢酶（ALDH）活性的机制来调节可卡因成瘾。

目的

基于这些先前的研究，我们调查了三种天然异黄酮，染料木黄酮、大豆苷元和染料木素，对可卡因强化效应的调节作用，以及在可卡因自我给药的操作性小鼠模型中线索诱导的复吸作用。

结果

慢性给予大豆苷元和染料木素治疗可减少获得可卡因静脉输注的操作性反应。另一方面，大豆苷元和染料木黄酮，但不是染料木素，可有效减少线索诱导的可卡因复吸。补充研究表明，大豆苷元对可卡因强化的作用是通过一种涉及多巴胺 2/3 型受体（DA-D2/3）活性的机制介导的。

结论

我们的结果表明，这些天然化合物单独或联合使用可能是治疗可卡因成瘾的一种潜在治疗方法。需要进一步的临床研究来确定它们的潜在治疗用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/7d7894123030/213_2021_5820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/9de2f6e4bb56/213_2021_5820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/457827d62084/213_2021_5820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/855a0248e2d9/213_2021_5820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/e802afbc4e7f/213_2021_5820_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/7d7894123030/213_2021_5820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/9de2f6e4bb56/213_2021_5820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/457827d62084/213_2021_5820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/855a0248e2d9/213_2021_5820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/e802afbc4e7f/213_2021_5820_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421b/8233246/7d7894123030/213_2021_5820_Fig5_HTML.jpg

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本文引用的文献

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