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.

尽管肥胖患病率很高，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 系统对神经信号传导的作用过程中，我们发现缺乏 translin/trax microRNA 降解酶的小鼠对安非他明表现出过度的运动反应。由于这些小鼠在正常体重的情况下表现出强烈的肥胖，我们检查了这种表型是否可能反映了脑内苯丙胺水平升高。为了评估这一假设，我们比较了野生型和Tsn KO 小鼠的血浆和脑安非他明水平。此外，我们还检查了饮食引起的肥胖增加对野生型小鼠血浆和脑内安非他明水平的影响。 Tsn KO 小鼠脑内苯丙胺水平高于野生型同窝小鼠，并且与肥胖相关。对野生型小鼠饮食引起的肥胖增加对大脑安非他明水平的影响的分析也表明，大脑安非他明水平与肥胖相关。 Tsn KO 小鼠或喂食高脂肪饮食的野生型小鼠表现出的肥胖增加与脑内安非他明水平升高相关。由于安非他明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，因此有必要进行进一步的研究来评估肥胖对这些患者安非他明水平的影响。