The alpha1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration.
The alpha1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration.
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DOI：
10.1016/j.pbb.2008.07.012
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发表时间：
2009-01
影响因子：
3.6
通讯作者：
Koob, George F.
中科院分区：
文献类型：
--
作者：
Greenwell, Thomas N.;Walker, Brendan M.;Cottone, Pietro;Zorrilla, Eric P.;Koob, George F.
先前的研究已经报道去甲肾上腺素能拮抗剂减轻阿片类戒断和依赖的一些症状。临床研究还表明，去甲肾上腺素能系统的修饰可能有助于保护患者免于复发。本研究验证了去甲肾上腺素能系统失调在依赖性大鼠海洛因自我给药中具有激励意义的假设。哌唑嗪，α1-肾上腺素能拮抗剂（0.5、1.0、1.5和2.0 mg/kg，i. p.），给予有有限（1小时/天;短期接触）或长期（12小时/天;长期接触）静脉内海洛因自我给药史的成年雄性Wistar大鼠。哌唑嗪剂量依赖性地减少海洛因自我管理的长期访问的大鼠，但不是短期访问的大鼠，与2 mg/kg的全身哌唑嗪显着减少1小时和2小时海洛因摄入量。哌唑嗪还逆转了与长期使用海洛因相关的膳食模式的一些变化，包括进食量较小和较短的膳食（3 h），同时还增加了总食物摄入量并减慢了膳食中的进食速度（3 h和12 h）。数据表明，α1-肾上腺素能系统可能有助于促进长期药物获取大鼠依赖性的机制，同时通过将膳食恢复到正常大小和持续时间来刺激其摄食。
Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration in dependent rats. Prazosin, an α1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). The data show that the α1-adrenergic system may contribute to mechanisms that promote dependence in rats with extended drug access, while also stimulating their food intake by restoring meals to the normal size and duration.
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影响因子：
3.6
作者：
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通讯作者：
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