Downregulation of κ-opioid receptors in basolateral amygdala and septum of rats withdrawn for 14 days from an escalating dose "Binge" cocaine administration paradigm
Downregulation of κ-opioid receptors in basolateral amygdala and septum of rats withdrawn for 14 days from an escalating dose "Binge" cocaine administration paradigm
复制标题
DOI：
10.1002/syn.20436
复制
发表时间：
2007-10-01
期刊：
影响因子：
2.3
通讯作者：
Kreek, Mary J.
中科院分区：
文献类型：
--
作者：
Bailey, Alexis;Gianotti, Robert;Kreek, Mary J.
有证据表明，阿片系统在可卡因成瘾中起着重要作用;很少有研究探讨它们在可卡因戒断中的作用。这项研究的目的是确定可卡因或长期戒断可卡因是否会改变K-阿片系统的受体成分。雄性Fischer大鼠注射生理盐水或可卡因（3 x 15 mg/kg/天，持续4天; 3 x 20 mg/kg/天，持续4天; 3 x 25 mg/kg/天，持续4天;以及3 x 30 mg/kg/天，持续2天），每天三次，间隔1小时，剂量递增，持续14天。相同处理的大鼠从可卡因或盐水中戒断14天。我们进行了定量放射自显影映射K-阿片受体（KOP-r）在大脑中的大鼠与这种递增剂量的“狂欢”可卡因管理模式和大鼠从可卡因撤出14天。在分析的所有区域均显示出显著的条件（慢性/戒断）效应。在用递增剂量狂欢可卡因给药模式处理的大鼠的隔膜中检测到[H-3]CI-977与KOP-r的结合显著增加，并在最后一次可卡因注射后30分钟处死。与此相反，有一个减少KOP-R结合在隔和基底外侧杏仁核的大鼠退出14天的慢性递增剂量的可卡因狂欢管理，相比，大鼠在14天的慢性递增剂量的可卡因管理结束。这些结果再次证实并扩展了KOP-r在慢性可卡因给药时的上调，剂量逐渐增加。在可卡因戒断动物的两个脑区中观察到的KOP-r结合降低可能导致停药后长时间报告的持续性烦躁不安。Synapse 61：820-826，2007. (C)2007 Wiley-Liss，Inc.
There is evidence showing that the opioid systems play an important role in cocaine addiction; fewer studies have examined their roles in cocaine withdrawal. This study was conducted to determine whether cocaine or chronic withdrawal from cocaine alters the receptor component of the K-opioid system. Male Fischer rats were injected with saline or cocaine (3 x 15 mg/kg/day for 4 days, 3 x 20 mg/kg/day for 4 days, 3 x 25 mg/kg/day for 4 days, and 3 x 30 mg/kg/day for 2 days), three times daily at 1-h intervals in an escalating dose paradigm for 14 days. Identically treated rats were withdrawn from cocaine or saline for 14 days. We performed quantitative autoradiographic mapping Of K-opioid receptors (KOP-r) in the brains of rats treated with this escalating dose "binge" cocaine administration paradigm and of rats withdrawn from cocaine for 14 days. A significant condition (chronic/withdrawal) effect was shown across all regions analyzed. A significant increase in [H-3]CI-977 binding to KOP-r was detected in the septum of rats treated with an escalating dose binge cocaine administration paradigm and killed 30 min after the last cocaine injection. In contrast, there was a decrease in KOP-r binding in the septum and the basolateral amygdala of rats withdrawn for 14 days from chronic escalating dose binge cocaine administration, compared to rats at the end of 14 days chronic escalating dose cocaine administration. These results reconfirm and extend that KOP-r undergoes upregulation in response to chronic binge cocaine administration here, with an escalating dose. The observed lowering in KOP-r binding, which was shown in two brain regions of cocaine withdrawn animals, might contribute to the persistent dysphoria reported a long time after the discontinuation of the drug. Synapse 61:820-826, 2007. (C) 2007 Wiley-Liss, Inc.