Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization
Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization
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DOI：
10.1124/jpet.107.122861
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发表时间：
2007-09-01
影响因子：
3.5
通讯作者：
Kalivas, Peter W.
中科院分区：
文献类型：
--
作者：
Knackstedt, Lori A.;Kalivas, Peter W.
随着时间的推移，吸毒成瘾者增加了吸毒的频率和数量。这一特征已经通过增加大鼠的药物摄入量来模拟，这些大鼠被给予长期接触可卡因的机会。然而，目前尚不清楚是否逐步增加药物摄入量或只是增加药物剂量的行为是这个模型的相关方面。本研究调查了吸毒升级现象是否会增强可卡因诱导的致敏作用和复发。训练大鼠在每天1小时的会议期间自我施用可卡因，持续7天。短期访问（ShA）组继续接受1小时的会议，10天，而一组大鼠切换到6小时的药物访问，长期访问（ShA-LgA）组，10天。此外，还增加了一个仅长时间使用（仅LgA）组，该组未接受预先培训，但仅给予10天的延长使用。ShA受试者维持稳定的药物摄入量; ShA-LgA受试者增加摄入量，而仅LgA受试者减少药物摄入量。在致敏和恢复试验中，所有组均显示出倒U形可卡因剂量-反应曲线。行为敏感化的表达在组间无差异。虽然两个长期接触组在比ShA组更多剂量的可卡因下表现出恢复，但升级的存在并不影响恢复。这些结果表明，延长获得可卡因自我管理产生的行为差异，相对于传统的短期访问动物的恢复，但不敏化。此外，预测恢复的差异更多的是通过可卡因的使用时间而不是通过药物摄入量的增加。
Cocaine addicts increase the frequency and amount of drug use over time. This characteristic has been modeled by escalating drug intake in rats that were given extended access to cocaine. However, it remains unclear whether the behavior of escalating drug intake or simply increased drug dose is the relevant aspect of this model. The present study investigated whether the phenomenon of escalated drug-taking enhances cocaine-induced sensitization and reinstatement. Rats were trained to self-administer cocaine during daily 1-h sessions for 7 days. A short-access (ShA) group continued to receive 1-h sessions for 10 days while a group of rats was switched to 6 h of drug access, long-access (ShA-LgA) group, for 10 days. In addition, a long-access only (LgA-only) group was added that was not pretrained but was only given extended access for 10 days. ShA subjects maintained stable drug intake; ShA-LgA subjects escalated intake while LgA-only subjects decreased drug intake. All groups displayed an inverted-U shaped cocaine dose-response curve in both the sensitization and reinstatement tests. There was no difference in the expression of behavioral sensitization between groups. Whereas both long-access groups showed reinstatement at more doses of cocaine than the ShA group, the presence of escalation did not affect reinstatement. These results indicate that extended access to cocaine self-administration produces behavioral differences relative to traditional short-access animals in reinstatement, but not sensitization. Furthermore, the differences in reinstatement are predicted more by length of cocaine access than by escalation of drug intake.