Elevated body fat increases amphetamine accumulation in brain: evidence from genetic and diet-induced forms of adiposity.
Elevated body fat increases amphetamine accumulation in brain: evidence from genetic and diet-induced forms of adiposity.
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DOI：
10.1038/s41398-021-01547-9
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发表时间：
2021-08-14
影响因子：
6.8
通讯作者：
Baraban JM
中科院分区：
文献类型：
--
作者：
Fu X;Shah AP;Keighron J;Mou TM;Ladenheim B;Alt J;Fukudome D;Niwa M;Tamashiro KL;Tanda G;Sawa A;Cadet JL;Rais R;Baraban JM
尽管肥胖症的发病率很高，但人们对其对精神药物药代动力学的潜在影响知之甚少。在研究microRNA系统在神经元信号传递中的作用的过程中，我们发现缺乏Translin/Trax microRNA降解酶的小鼠对苯丙胺表现出夸大的运动反应。由于这些小鼠在正常体重的情况下表现出强烈的肥胖症，我们检查了这种表型是否反映了脑部苯丙胺水平的升高。为了验证这一假说，我们比较了野生型和TSN KO小鼠的血浆和脑内苯丙胺水平。此外，我们还检查了饮食诱导的肥胖增加对野生型小鼠血浆和脑内苯丙胺水平的影响。TSN KO小鼠的脑部苯丙胺水平高于野生型小鼠，并与肥胖相关。分析饮食诱导的野生型小鼠肥胖增加对大脑苯丙胺水平的影响也表明，大脑苯丙胺水平与肥胖相关。TSN KO小鼠或喂食高脂饮食的野生型小鼠表现出的肥胖增加与脑部苯丙胺水平的升高有关。由于苯丙胺及其类似物被广泛用于治疗与肥胖相关的注意力缺陷障碍，有必要进行进一步的研究，以评估肥胖对这些患者苯丙胺水平的影响。
Despite the high prevalence of obesity, little is known about its potential impact on the pharmacokinetics of psychotropic drugs. In the course of investigating the role of the microRNA system on neuronal signaling, we found that mice lacking the translin/trax microRNA-degrading enzyme display an exaggerated locomotor response to amphetamine. As these mice display robust adiposity in the context of normal body weight, we checked whether this phenotype might reflect elevated brain levels of amphetamine. To assess this hypothesis, we compared plasma and brain amphetamine levels of wild type and Tsn KO mice. Furthermore, we checked the effect of diet-induced increases in adiposity on plasma and brain amphetamine levels in wild type mice. Brain amphetamine levels were higher in Tsn KO mice than in wild type littermates and correlated with adiposity. Analysis of the effect of diet-induced increases in adiposity in wild type mice on brain amphetamine levels also demonstrated that brain amphetamine levels correlate with adiposity. Increased adiposity displayed by Tsn KO mice or by wild type mice fed a high-fat diet correlates with elevated brain amphetamine levels. As amphetamine and its analogues are widely used to treat attention deficit disorder, which is associated with obesity, further studies are warranted to assess the impact of adiposity on amphetamine levels in these patients.
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影响因子：
25
作者：
Im, Heh-In;Hollander, Jonathan A.;Bali, Purva;Kenny, Paul J.
通讯作者：
Kenny, Paul J.
影响因子：
2.9
作者：
Davidson TL;Monnot A;Neal AU;Martin AA;Horton JJ;Zheng W
通讯作者：
Zheng W
影响因子：
3.6
作者：
Park AJ;Shetty MS;Baraban JM;Abel T
通讯作者：
Abel T
DOI：
10.1177/0269881113482532
发表时间：
2013-06
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Heal DJ;Smith SL;Gosden J;Nutt DJ
通讯作者：
Nutt DJ
影响因子：
8.1
作者：
Fu, Xiuping;Shah, Aparna P.;Baraban, Jay M.
通讯作者：
Baraban, Jay M.