Prolonged daily exposure to IV cocaine results in tolerance to its stimulant effects
Prolonged daily exposure to IV cocaine results in tolerance to its stimulant effects
复制标题
DOI：
10.1016/j.pbb.2005.09.013
复制
发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Ettenberg, A
中科院分区：
文献类型：
--
作者：
Ben-Shahar, O;Moscarello, JM;Ettenberg, A
我们之前已经证明，每天静脉注射可卡因 1 小时（而非 6 小时）会在戒断 14 天后诱导对静脉注射可卡因激发的敏化反应。在这里，我们尝试使用IP可卡因挑战来复制这些结果，并添加一组每天接触可卡因1小时的动物，但维持与盐水动物（即Coc组）相当的给药水平。由于与成瘾相关的神经适应特别持久，我们还测试了 60 天较长戒断期后对可卡因挑战的反应。在 8 天的时间里，大鼠每天静脉注射生理盐水或可卡因 1 小时 (Coclh)，或可卡因 6 小时 (Coc6h)。随后，停药 14 天后，只有 Coc 动物对腹腔注射可卡因攻击表现出敏化运动反应。戒断60天后，IP可卡因未能在Coc 1h动物中产生致敏反应，但在Coc6h动物中产生耐受反应。目前的数据支持这样的观点，即每天服用 6 小时的可卡因会导致与每天服用 1 小时的药物所产生的神经适应不同的神经适应。此外，这些数据进一步证明可卡因致敏和成瘾之间存在分离。 (C) 2005 Elsevier Inc. 保留所有权利。
We have previously shown that 1 h, but not 6 h, of daily access to IV cocaine induces a sensitized response to IV cocaine challenge after 14 days of withdrawal. Here we tried to replicate these results using an IP cocaine challenge and adding a group of animals that had 1 h daily access to cocaine, but maintained levels of administration comparable to that of saline animals (i.e. a Coc group). Since addiction-associated neuroadaptations are particularly long lasting, we also tested the response to cocaine challenge after a longer withdrawal period of 60 days. Rats had daily access to IV self-administered saline or cocaine for 1 h (Coclh), or to cocaine for 6 h (Coc6h) over 8 days. Subsequently, after 14 days of withdrawal only Coc animals showed a sensitized locomotor response to cocaine challenge administered IP. After 60 days of withdrawal, IP cocaine failed to produce a sensitized response in Coc 1h animals and produced a tolerant response in Coc6h animals. The present data support the notion that 6 h of daily access to cocaine leads to different neuroadaptations than those resulting from 1 h of daily access to the drug. In addition, these data further demonstrate a dissociation between sensitization and addiction to cocaine. (C) 2005 Elsevier Inc. All rights reserved.