Persistent Upregulation of μ-opioid, but not adenosine, receptors in brains of long-term withdrawn escalating dose "Binge" cocaine-treated rats
Persistent Upregulation of μ-opioid, but not adenosine, receptors in brains of long-term withdrawn escalating dose "Binge" cocaine-treated rats
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DOI：
10.1002/syn.20168
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发表时间：
2005-09-01
期刊：
影响因子：
2.3
通讯作者：
Kreek, MJ
中科院分区：
文献类型：
--
作者：
Bailey, A;Gianotti, R;Kreek, MJ
有证据表明，阿片和腺苷系统在可卡因成瘾中起着重要作用；很少有研究研究它们在可卡因戒断中的作用。为了确定可卡因和/或慢性戒断可卡因是否改变了阿片和腺苷系统的特定成分，我们对接受递增剂量“狂欢”可卡因给药模式的大鼠和慢性戒断可卡因的大鼠大脑中的u-阿片受体、A(1)和A(2A)腺苷受体进行了定量放射自显影成像。雄性Fischer大鼠注射生理盐水或可卡因(15×3 mg/kg/d×4d，20×3 mg/kg/d×4d，25×3 mg/kg/d×4d，30×3 mg/kg/d×2d)，间隔1h，连续14d。类似处理的大鼠被从该范例中撤出14天。在长期戒断的大鼠和慢性可卡因治疗的大鼠中，在额叶和扣带回皮质以及尾壳核中检测到[~3H]DAMGO与p受体的结合显著增加。在分析的任何区域中，都没有发现可卡因诱导的A或A2a受体结合的显著变化。这些结果再次证实了Mu-阿片(MOP)受体在慢性剂量“狂欢”可卡因注射后表达上调。这种上调首次被证明在戒毒后至少持续14天，在“狂欢”可卡因升级之后。(C)2005年Wiley-Liss，Inc.
There is evidence showing that the opioid and adenosine systems play an important role in cocaine addiction; fewer studies have examined their roles in cocaine withdrawal. To determine whether cocaine and/or chronic withdrawal from cocaine alters the specific components of the opioid and adenosine systems, we carried out quantitative autoradiographic mapping of mu-opioid, A(1) and A(2A) adenosine receptors in the brains of rats treated with an escalating dose "binge" cocaine administration paradigm and of rats chronically withdrawn from cocaine. Male Fischer rats were injected with saline or cocaine (15 x 3 mg/kg/day for 4 days, 20 x 3 mg/kg/day for 4 days, 25 x 3 mg/kg/day for 4 days and 30 x 3 mg/kg/day for 2 days) at 1-h intervals for 14 days. Similarly treated rats were withdrawn from that paradigm for 14 days. A significant increase in [3 H]DAMGO binding to p-receptors was detected in the frontal and cingulate cortex, as well as in the caudate putamen, of long-term withdrawn rats after an escalating dose "binge" cocaine administration paradigm and in chronic cocaine-treated rats. No significant cocaine-induced change was found in A, or A2A receptor binding in any region analyzed. These results reconfirm that mu-opioid (MOP) receptors undergo upregulation in response to chronic escalating dose "binge" cocaine administration. This upregulation was shown for the first time to persist at least 14 days into withdrawal after escalating "binge" cocaine. (c) 2005 Wiley-Liss, Inc.