Blockade of THC-Seeking Behavior and relapse in monkeys by the cannabinoid CB1-Receptor antagonist rimonabant
Blockade of THC-Seeking Behavior and relapse in monkeys by the cannabinoid CB1-Receptor antagonist rimonabant
复制标题
DOI：
10.1038/npp.2008.21
复制
发表时间：
2008-11-01
影响因子：
7.6
通讯作者：
Goldberg, Steven R.
中科院分区：
文献类型：
--
作者：
Justinova, Zuzana;Munzar, Patrik;Goldberg, Steven R.
越来越多的证据表明，内源性大麻素系统调节环境线索诱导对药物的寻求能力，包括尼古丁和酒精。然而，很少有人关注将这些进展扩展到日益严重的大麻使用障碍问题。因此，我们研究了大麻的主要精神活性成分德尔塔(9)-四氢大麻酚（THC）的静脉自我给药，采用二级药物寻求计划。松鼠猴的杠杆反应只产生一个短暂的提示光，直到实验结束，最后的反应伴随着提示发出了四氢大麻酚。在戒断一段时间后，当使用恢复程序来模拟复发时，四氢大麻酚寻求行为通过提示或预先给予四氢大麻酚，其他大麻素激动剂或吗啡而不是可卡因而强有力地恢复。大麻素拮抗剂利莫那班阻断了线索诱导的寻药作用、四氢大麻酚诱导的寻药作用和四氢大麻酚的直接强化作用。因此，利莫那班和相关药物可能是有效的治疗大麻素依赖。
Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.