Characterization of cocaine self-administration and pharmacokinetics as a function of time of day in the rat
Characterization of cocaine self-administration and pharmacokinetics as a function of time of day in the rat
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DOI：
10.1016/s0091-3057(99)00207-5
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发表时间：
2000-02-01
影响因子：
3.6
通讯作者：
Gauvin, DV
中科院分区：
文献类型：
--
作者：
Baird, TJ;Gauvin, DV
两个实验检查了一天中的时间对雄性斯普拉格·道利大鼠静脉注射可卡因的影响及其相关的药代动力学特征。两种实验均将大鼠按每天0100、0700、1300、1900四个时段随机分为实验组（n = 6/组），进行实验程序。在这两个实验中，大鼠都被维持在12 L:12 D的环境光照周期中，在0600小时开灯。因此，在光照和黑暗阶段分别进行1（0700,1900）或7（1300,0100）小时的训练和测试。在实验1中，评估了行为活性剂量范围内可卡因自我给药的特征。在四个实验组中，在自我给药率和模式上观察到统计学上的显著差异，最显著的特征是可卡因剂量的明显变化，这产生了反应率的峰值。具体来说，在0100和1300h测试的组似乎对低剂量可卡因的强化特性表现出更强的敏感性，相对于0700和1900小时测试的组。观察到的实验对象对低剂量可卡因表观敏感性的差异与一般运动活动的持续模式没有任何简单的关系。在上述四个采样周期中，静脉输注（1.8 mg/kg）后1小时内评估可卡因的药代动力学特征时，没有出现相应的差异。(C) 2000 Elsevier Science Inc.；
Two experiments examined the influence of time of day on the intravenous self-administration of cocaine and its associated pharmacokinetic profile in male Sprague Dawley rats. In both experiments, individual rats were randomly assigned to experimental groups (n = 6/group) according to four selected times of day, 0100, 0700, 1300, and 1900 h, during which experimental procedures were conducted. In both experiments, rats were maintained under a 12 L:12 D ambient lighting cycle, with lights on at 0600 h. Training and testing was thus conducted either 1 (0700, 1900) or 7 (1300, 0100 h) hours into the light and dark phases. In Experiment 1, characteristics of cocaine self-administration across a behaviorally active dose range were assessed. Statistically significant differences were observed in the rates and patterns of self-administration across the four experimental groups, most notably characterized by an apparent shift in the dose of cocaine, which engendered peak rates of responding. Specifically, groups tested at 0100 and 1300 h appeared to exhibit enhanced sensitivity to the reinforcing properties of low-dose cocaine relative to groups tested at 0700 and 1900 h. The observed differences in apparent sensitivity of experimental subjects to low-dose cocaine were not related in any simple way to ongoing patterns of general locomotor activity, and were not accompanied by corresponding variance in the pharmacokinetic profiles of cocaine when assessed over 1 h following an intravenous infusion (1.8 mg/kg) at each of the four sampling periods noted above. (C) 2000 Elsevier Science Inc.