Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens
Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens
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DOI：
10.1038/sj.npp.1300748
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发表时间：
2005-08-01
影响因子：
7.6
通讯作者：
Carelli, RM
中科院分区：
文献类型：
--
作者：
Hollander, JA;Carelli, RM
人类可卡因成瘾的特征是戒断吸毒和复发的周期。在这里，电生理记录程序被用来确定是否中断和恢复可卡因自我管理后，神经核（Acb）的神经元放电特性被改变。训练大鼠（n=12）自我施用可卡因（每天2小时），然后分成两组。在接下来的2天内完成的另外两个自我给药阶段（试验阶段1和2）期间，记录组1（对照组）的ACB活性。在第二天完成的一次自我给药期间（试验1）和1个月后的第二次自我给药期间（试验2），记录组2（1个月）的ACB活性。在以前的报告中，一个子集的Acb神经元表现出模式化的放电（短时间和/或长期的周期性变化，称为“阶段性活动”）相对于可卡因强化的反应在测试会话1。值得注意的是，相活性细胞的百分比显着增加（近两倍）1个月的禁欲后，在核心，但不是外壳的Acb。同样，神经相关性的强度（通过信号与基线比率确定）也随着禁欲而增加。在另一组大鼠（n=12）中进行的灭绝实验显示，禁欲后药物的动机状态增加。结果表明，从可卡因自我管理的禁欲导致编码可卡因相关信息的Acb神经元的数量和强度急剧增加，从而代表了第一个神经生理学相关的“大脑奖励系统”的高度激活后，禁欲和恢复（复发）可卡因消费。
Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n=12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n=12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption.