Dataset for: Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 versus 90-100 seconds promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5-90 seconds produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely-moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 seconds. We measured cocaine concentrations in the dorsal striatum using rapid-sampling microdialysis (1 sample/minute) and high-performance liquid chromatography-tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of non-dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5-second infusions. We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5-second infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.成瘾性药物抵达大脑的速度越快，成瘾风险便越高。即便药物递送速率仅存在微小差异，也会对实验结果产生影响。以5秒与90-100秒的时长分别静脉输注可卡因，可增强该药物的精神运动与奖赏动机效应敏化，并优先激活中脑皮层边缘系统（mesocorticolimbic regions）。目前仍不清楚此类效应究竟源于药物抵达大脑的速度差异、剂量差异，还是二者共同作用。本研究推测，将静脉输注可卡因的速率控制在5秒至90秒之间，可使脑内药物浓度的上升速率产生差异，但二者的峰值浓度保持一致。实验对象为自由活动的雄性Wistar大鼠，分别以5秒、45秒及90秒的时长接受单次静脉可卡因输注（单次剂量为2.0 mg/kg）。我们采用快速采样微透析（rapid-sampling microdialysis，1样本/分钟）结合高效液相色谱-串联质谱（high-performance liquid chromatography-tandem mass spectrometry）技术，检测了背侧纹状体（dorsal striatum）内的可卡因浓度，同时还检测了多巴胺及其他神经化学物质的胞外浓度。无论输注速率如何，单次可卡因给药均未改变非多巴胺能神经化学物质的浓度。输注速率对可卡因及多巴胺的峰值浓度无显著影响，但5秒输注组的浓度上升速度更快。我们还基于可卡因输注速率评估了其精神运动活性变化，结果显示输注速率对总运动距离无显著影响，但5秒输注组的运动启动时间更早。由此可见，可卡因递送速率的微小差异，不仅会影响药物与多巴胺浓度的上升速率，还会改变精神运动活性。药物与多巴胺浓度的更快上升速率，或许是快速输注可卡因更易成瘾的关键机制之一。