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[ F]可卡因使用后运动活动对 C57Bl/6 雄性小鼠脑 FDG 摄取的影响:小动物正电子发射断层扫描研究。

[ F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study.

机构信息

Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

Laboratory of Nuclear Medicine, Department of Radiology and Oncology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

出版信息

J Neurosci Res. 2022 Oct;100(10):1876-1889. doi: 10.1002/jnr.25102. Epub 2022 Jul 2.

Abstract

We verified if cocaine-induced peripheral activation might disrupt [ F]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [ F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [ F]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [ F]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [ F]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [ F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.

摘要

我们验证了可卡因引起的外周激活是否会在可卡因挑战后破坏 [ F]FDG 脑摄取,并提出了一种测量小鼠可卡因引起的脑代谢改变的最佳方案。雄性 C57Bl/6 小鼠注射 [ F]FDG 后,随机分为三组。第 1 组和第 2 组在给予 [ F]FDG 后保持清醒,5 分钟后给予生理盐水或可卡因(20mg/kg)。第 1 组(n=5)的动物随后在开放场中评估 30 分钟,第 2 组(n=6)的动物在同一时间内单独留在笼中。给予 [ F]FDG 后 45 分钟,采集图像 30 分钟。第 3 组(n=6)保持麻醉状态,在示踪剂注射后立即开始采集图像,持续 75 分钟。在开始采集后 5 分钟,给予生理盐水(第 1 天)或可卡因(第 2 天)。另一组动物(n=5)每天接受可卡因或生理盐水(n=6)治疗 10 天,并使用动态方案进行扫描以验证其疗效。与基线相比,只有在麻醉状态下的动物中,给予可卡因后 [ F]FDG 摄取增加。在开放场或笼中保持的动物中未观察到可卡因对大脑的影响。使用麻醉是通过 [ F]FDG PET 观察可卡因引起的大脑代谢变化所必需的,为研究未受干扰的对象提供了一种有趣的临床前方法,并能够进行双向转化科学研究,以更好地理解可卡因使用障碍。

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