Fast onset of dopamine uptake inhibition by intravenous cocaine
Fast onset of dopamine uptake inhibition by intravenous cocaine
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DOI：
10.1111/j.1460-9568.2004.03736.x
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Jones, SR
中科院分区：
文献类型：
--
作者：
Mateo, Y;Budygin, EA;Jones, SR
采用体内伏安法观察麻醉大鼠伏隔核内静脉注射可卡因对多巴胺摄取抑制作用的发生时间。关于可卡因作用的时间过程，行为研究和神经化学研究之间存在分歧。由于伏安法的高时间分辨率，多巴胺释放和摄取的过程可以在时间上分离，从而更容易评估可卡因对摄取的影响。静脉注射可卡因（1.5 mg/kg）后4 s内，多巴胺摄取明显受到抑制，并在20 s内达到平台期。电诱发多巴胺信号的峰值高度也迅速增加可卡因。信号在大约1小时内恢复到基线值。在平行的行为研究中，在静脉输注可卡因后的5-6秒内，运动活动显著增加。在这里，我们证明静脉注射可卡因在几秒钟内开始抑制多巴胺的摄取。这比之前的神经化学估计至少快了10倍。目前的研究结果可能有助于理解可卡因早期行为反应的神经生物学机制。
In vivo voltammetry in the nucleus accumbens of anesthetized rats was used to investigate the time of onset of dopamine uptake inhibition by intravenous cocaine. There is disagreement between behavioral and neurochemical studies concerning the time-course of cocaine effects. Because of the high temporal resolution of voltammetry, the processes of dopamine release and uptake could be temporally separated to make evaluation of cocaine effects on uptake easier to address. Within 4 s after intravenous cocaine administration (1.5 mg/kg) there was significant inhibition of dopamine uptake that reached a plateau in 20 s. The peak heights of electrically evoked dopamine signals were also rapidly increased by cocaine. The signals returned to baseline values within approximately 1 h. In parallel behavioral studies, locomotor activity was significantly increased within 5-6 s following intravenous infusion of cocaine. Here we demonstrate that intravenous cocaine administration begins inhibiting the uptake of dopamine within a few seconds. This is at least 10-fold faster than previous neurochemical estimates. The present findings may contribute to the understanding of the neurobiological mechanisms underlying the early behavioral responses to cocaine.