Distribution and clearance of cocaine in brain is influenced by genetics
Distribution and clearance of cocaine in brain is influenced by genetics
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DOI：
10.1016/s0091-3057(97)00471-1
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发表时间：
1998-03-01
影响因子：
3.6
通讯作者：
Jones, BC
中科院分区：
文献类型：
--
作者：
Azar, MR;Acar, N;Jones, BC
本研究的目的是研究可卡因在两个近交系小鼠C57 BL/6（B6）和DBA/2（D2）体内的药代动力学。雄性和雌性小鼠IP给予30 mg/kg可卡因，并在注射后5、15、30或60分钟后处死。迅速取出大脑，测定大脑中可卡因的总浓度。使用气相色谱法和质谱法对可卡因进行定量。本研究的结果揭示了全脑可卡因动力学的应变差异。具体而言，我们观察到，在5分钟后，Bt小鼠从大脑中清除可卡因，t（1/2）估计为22.3分钟，而D2小鼠中的分布似乎直到15分钟才不完全，随后的t（1/2）估计为11.2分钟。这些结果表明，尽管D2小鼠的清除速度更快，在该品系中延长的分布时间可能有助于解释为什么与B6小鼠相比，D2小鼠显示出由可卡因引起的更大的初始运动激活。(C)1998年爱思唯尔科学公司
The purpose of this study was to examine the pharmacokinetics of cocaine in two inbred mouse strains, C57BL/6 (B6) and DBA/2 (D2). Male and female mice were administered 30 mg kg(-1) cocaine IP and killed after 5, 15, 30, or 60 minutes postinjection. Brains were removed quickly and assayed for total brain cocaine concentration. Quantification of cocaine was conducted using gas chromatography and mass spectrometry. The results of this study revealed a strain difference in total brain cocaine kinetics. Specifically, we observed that at 5 min onward, Bt mice cleared cocaine from the brain with a t(1/2) estimated at 22.3 min, while distribution in D2 mice appeared to be incomplete until 15 min with a subsequent t(1/2) estimated at 11.2 min. These results show that despite faster clearance by D2 mice, the prolonged time to distribution in this strain may help explain why D2 mice show initial greater locomotor activation by cocaine, compared to B6s. (C) 1998 Elsevier Science Inc.