Antibiotic Knockdown of Gut Bacteria Sex-Dependently Enhances Intravenous Fentanyl Self-Administration in Adult Sprague Dawley Rats.
Antibiotic Knockdown of Gut Bacteria Sex-Dependently Enhances Intravenous Fentanyl Self-Administration in Adult Sprague Dawley Rats.
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DOI：
10.3390/ijms24010409
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发表时间：
2022-12-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
大脑和肠道细菌之间的交流会影响药物和成瘾相关行为。为了研究肠道微生物群对芬太尼强化和奖励的作用，我们使用口服不可吸收的抗生素鸡尾酒耗尽成年Sprague道利雄性和雌性大鼠的肠道细菌，并允许大鼠静脉内自我施用芬太尼，以逐步增加强化时间表。我们发现，抗生素治疗在最低强化时间表（即，固定比率1）。接受抗生素治疗的男性和女性在更高的强化时间表中自我施用更大量的芬太尼。然后，我们通过短链脂肪酸给药来补充微生物代谢物，以评估肠-脑通信中的潜在机制，并发现恢复代谢物可将芬太尼自我给药降低到更高固定比例强化时间表的对照组。我们的研究结果强调了成年大鼠中肠道细菌代谢产物的敲除和拯救与芬太尼自我给药之间的重要关系，这为肠道微生物组与阿片类药物使用之间的重要关系提供了支持。在这一领域的进一步工作可能会导致有效的，有针对性的治疗类阿片相关疾病的干预措施。
Communication between the brain and gut bacteria impacts drug- and addiction-related behaviors. To investigate the role of gut microbiota on fentanyl reinforcement and reward, we depleted gut bacteria in adult Sprague Dawley male and female rats using an oral, nonabsorbable antibiotic cocktail and allowed rats to intravenously self-administer fentanyl on an escalating schedule of reinforcement. We found that antibiotic treatment enhanced fentanyl self-administration in males, but not females, at the lowest schedule of reinforcement (i.e., fixed ratio 1). Both males and females treated with antibiotics self-administered greater amounts of fentanyl at higher schedules of reinforcement. We then replete microbial metabolites via short-chain fatty acid administration to evaluate a potential mechanism in gut-brain communication and found that restoring metabolites decreases fentanyl self-administration back to controls at higher fixed ratio schedules of reinforcement. Our findings highlight an important relationship between the knockdown and rescue of gut bacterial metabolites and fentanyl self-administration in adult rats, which provides support for a significant relationship between the gut microbiome and opioid use. Further work in this field may lead to effective, targeted treatment interventions in opioid-related disorders.
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DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.3
作者：
Freedman, Zachary G.;Kane, Jennifer A.;Graziane, Nicholas M.
通讯作者：
Graziane, Nicholas M.
影响因子：
3.6
作者：
Cicero, TJ;Aylward, SC;Meyer, ER
通讯作者：
Meyer, ER
影响因子：
10.6
作者：
Burokas, Aurelijus;Arboleya, Silvia;Cryan, John F.
通讯作者：
Cryan, John F.
影响因子：
64.5
作者：
Han W;Tellez LA;Perkins MH;Perez IO;Qu T;Ferreira J;Ferreira TL;Quinn D;Liu ZW;Gao XB;Kaelberer MM;Bohórquez DV;Shammah-Lagnado SJ;de Lartigue G;de Araujo IE
通讯作者：
de Araujo IE