Disulfiram facilitates the development and expression of locomotor sensitization to cocaine in rats
Disulfiram facilitates the development and expression of locomotor sensitization to cocaine in rats
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DOI：
10.1016/s0006-3223(03)00241-5
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发表时间：
2003-11-01
影响因子：
10.6
通讯作者：
Kosten, TA
中科院分区：
文献类型：
--
作者：
Haile, CN;During, MJ;Kosten, TA
背景资料：双硫仑（DS; Antabuse）抑制多巴胺-β-羟化酶，导致大脑多巴胺水平增加，并对可卡因成瘾显示出治疗功效。然而，很少有临床前研究已经进行。本研究建立了DS对可卡因在大鼠中运动敏化的影响。方法：大鼠单独或联合给予溶媒、可卡因（10 mg/kg;腹膜内[IP]）或DS（50或100 mg/kg; IP）5天（发育期）。每天测量自发活动60分钟。在10天的药物洗脱后，向大鼠施用可卡因，并测量自发活动（表达期）。在连续5天给予两种可卡因剂量（0或10 mg/kg）之一和两种DS剂量（0或100 mg/kg）之一的单独大鼠组中评估血浆可卡因水平。10天后，收集血液60分钟postcocaine injection.Results：可卡因自发致敏的发展是由DS促进，即使DS单独活动水平的影响很小。此外，表达的致敏作用是最大的大鼠先前给予DS，不能归因于改变血浆可卡因levels.Conclusions的影响：由于DS显示可卡因成瘾的治疗效果，本研究的结果表明，潜在的治疗药物应增强，而不是减弱，大鼠运动致敏。(C)2003生物精神病学学会。
Background: Disulfiram (DS; Antabuse) inhibits dopamine- beta-hydroxylase leading to increased brain dopamine levels and shows treatment efficacy for cocaine addiction. Yet few preclinical studies have been performed. This study establishes the effects of DS on locomotor sensitization to cocaine in rats.Methods: Rats were administered vehicle, cocaine (10 mg/kg; intraperitoneally [IP]), or DS (50 or 100 mg/kg; IP) alone or in combination for 5 days (development phase). Locomotor activity was measured for 60-min each day. After a 10-day drug washout, rats were administered cocaine, and locomotor activity was measured (expression phase). Plasma cocaine levels were assessed in separate groups of rats administered one of two cocaine doses (0 or 10 mg/kg) and one of two DS doses (0 or 100 mg/kg) for 5 days. Ten days later, blood was collected 60-min postcocaine injection.Results: The development of cocaine locomotor sensitization was facilitated by DS even though DS alone had minimal effect on activity levels. Furthermore, expression of sensitization was greatest in rats previously administered DS, an effect that cannot be attributed to altered plasma cocaine levels.Conclusions: Because DS shows treatment efficacy for cocaine addiction, results from this study suggest potential treatment agents should enhance, not attenuate, locomotor sensitization in rats. (C) 2003 Society of Biological Psychiatry.