Acute and chronic dopamine dynamics in a nonhuman primate model of recreational cocaine use
Acute and chronic dopamine dynamics in a nonhuman primate model of recreational cocaine use
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DOI：
10.1523/jneurosci.20-18-07109.2000
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发表时间：
2000-09-15
影响因子：
5.3
通讯作者：
Bradberry, CW
中科院分区：
文献类型：
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作者：
Bradberry, CW
使用模型的娱乐可卡因消费，我们已经确定在四个恒河猴的影响，自我管理的可卡因中脑边缘和感觉运动纹状体多巴胺能神经传递。通过使用固定比例自我给药和微透析程序，确定了在6个月内自我给药和跨多个给药期重复可卡因的影响。可卡因暴露量适中，每周最多允许输注两次0.5 mg/kg。在可卡因自我给药期间，观察到对可卡因提高细胞外纹状体多巴胺的能力的急性耐受性。在6个月的重复自我给药期间，固定剂量对细胞外多巴胺的影响显著增加，表明灵长类动物对自我给药可卡因的影响发生神经化学致敏。一个显着的多巴胺能反应noncontingent可卡因也被观察到，没有增加细胞外多巴胺在响应一个意想不到的盐水替代，表明神经化学反应自我管理的可卡因主要是由药物的直接药理作用，而不是通过调节外部环境的线索。这些结果突出了可卡因的神经化学反应性的时间依赖性变化的对比，这取决于是否进行了会话内或会话之间的比较。他们还证明，可卡因消费的娱乐水平可能导致神经化学敏感，这是一种可能导致成瘾的大脑功能的持久变化。
Using a model of recreational cocaine consumption, we have determined in four rhesus monkeys the impact of self-administered cocaine on mesolimbic and sensorimotor striatal dopaminergic neurotransmission. The effects of cocaine repeated within a self-administration session and across multiple sessions over a 6 month period were determined by the use of fixed-ratio self-administration and microdialysis procedures. The exposure to cocaine was modest, with at most two 0.5 mg/kg infusions permitted in each weekly session. Within a cocaine self-administration session, acute tolerance to the ability of cocaine to elevate extracellular striatal dopamine was observed. Over a period of 6 months of repeated self-administration, there was a significant increase in the impact of a fixed dose on extracellular dopamine, indicating that neurochemical sensitization to the effects of self-administered cocaine occurs in primates. A pronounced dopaminergic response to noncontingent cocaine was also observed, with no increases in extracellular dopamine in response to an unexpected saline substitution, indicating that the neurochemical response to self-administered cocaine is primarily caused by direct pharmacological effects of the drug rather than by conditioning to external environmental cues. These results highlight the contrast in time-dependent changes in neurochemical responsiveness to cocaine, depending on whether within-session or between-session comparisons are made. They also demonstrate that recreational levels of cocaine consumption can result in neurochemical sensitization, an enduring change in brain function that may contribute to addiction.