Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats
Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats
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DOI：
10.1016/s0306-4522(00)00168-8
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Rebec, GV
中科院分区：
文献类型：
--
作者：
Kiyatkin, EA;Kiyatkin, DE;Rebec, GV
一种新的方法结合快速扫描循环伏安法与离子电渗多巴胺传递被用于在自由行为的大鼠中，以评估在已知维持自我管理行为的剂量（1.0 mg/kg）下静脉注射可卡因诱导的丘脑核多巴胺摄取抑制的时间过程。可卡因显著增加了多巴胺反应的衰减时间，而没有改变其幅度或达到峰值的时间。衰减时间的增加在2分钟时是明显的，在6分钟时达到峰值（+87%），并且在单次可卡因注射后18分钟时降低至基线。衰减时间的变化在所有大鼠中是相似的，并且对于在一个会话内和重复会话内的后续可卡因注射，基本上保持相同，尽管稍大。多巴胺衰减时间的变化并没有与可卡因诱导的运动激活，这是最大的注射后的第一分钟，并在接下来的20分钟内缓慢下降。我们的数据提供了直接的证据，在行为相关的条件下，静脉注射可卡因诱导的多巴胺摄取的阶段性变化。相对缓慢和逐渐发展的多巴胺摄取抑制，峰值时，表现大鼠自我注射可卡因，是不一致的建议的作用，这种机制在急性奖励（欣快）的影响，自我注射可卡因，但支持其作用的激活和动机方面的药物寻求和吸毒行为。由于静脉注射可卡因迅速进入大脑，并在有效抑制多巴胺摄取（6分钟）之前很久就在神经组织中达到峰值（1-2分钟），因此似乎这种药物的一些急性精神情感（“冲动”）、行为、自主神经和神经元效应（这些效应显然对多巴胺受体阻滞具有抗性）是通过快速中枢或外周机制介导的，而不依赖于单胺摄取。出版社：Elsevier Science Ltd
A new approach combining fast-scan cyclic voltammetry with iontophoretic dopamine delivery was used in freely behaving rats to evaluate the time-course of dopamine uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose (1.0 mg/kg) known to maintain self-administration behavior. Cocaine significantly increased the decay time of the dopamine response without altering its magnitude or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min (+ 87%), and decreased to baseline at 18 min after a single cocaine injection. The change in decay time was similar in all rats and remained essentially the same, albeit slightly larger, for subsequent cocaine injections both within a session and over repeated sessions. The change in dopamine decay time did not correlate with cocaine-induced motor activation, which was maximal during the first minute after injection and decreased slowly over the next 20 min.Our data provide direct evidence for a phasic change in dopamine uptake induced by intravenous cocaine under behaviorally relevant conditions. The relatively slow and gradual development of dopamine uptake inhibition, which peaks at times when behaving rats self-inject cocaine, is inconsistent with the suggested role of this mechanism in the acute rewarding (euphoric) effects of self-injected cocaine, but supports its role in the activational and motivational aspects of drug-seeking and drug-taking behavior. Because intravenous cocaine enters the brain rapidly and peaks in neural tissue (1-2 min) long before it effectively inhibits dopamine uptake (6 min), it appears that some of the acute psychoemotional ("rush"), behavioral, autonomic, and neuronal effects of this drug, which are apparently resistant to dopamine receptor blockade, are mediated via rapid central or peripheral mechanisms independent of monoamine uptake. Published by Elsevier Science Ltd.