Knackstedt L A, Ettenberg A
Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106, USA.
Psychopharmacology (Berl). 2005 Mar;178(2-3):143-50. doi: 10.1007/s00213-004-1996-2. Epub 2004 Aug 25.
Human drug users report that the initial positive effects of cocaine are followed by a dysphoric state characterized by anxiety and drug-craving. As a means of presumably attenuating these negative aftereffects, 50-90% of cocaine users choose to co-administer ethanol during cocaine binges. This co-administration reportedly prolongs the "high" and diminishes the "low" associated with cocaine use.
The current study was intended to assess whether this phenomenon could be modeled in the animal laboratory. We have previously shown that animals running a straight alley for an intravenous cocaine reward develop a unique approach-avoidance "conflict" behavior that is characterized by stop and retreat behaviors as the subjects approach the goal box. The retreats are thought to reflect the concurrent positive (reward) and negative (anxiety) associations with the goal box and can be dose-dependently reduced by pretreatment with diazepam, which presumably attenuates the anxiety stemming from the conflict.
To test the role of ethanol in reducing cocaine-induced anxiety, rats were trained to run a straight-arm alley for a single daily injection of cocaine (1.0 mg/kg IV).
Rats that had the opportunity to then drink either an 8% or a 4% sucrose-ethanol solution immediately following their daily runway trial came to exhibit fewer retreats than rats that did not drink ethanol following their cocaine injection.
These results suggest that ethanol effectively reduces the development of approach-avoidance conflict in animals running an alley for IV cocaine, a result that may account for the prevalence of cocaine-ethanol co-administration in humans.
吸食毒品的人报告称,可卡因最初产生的积极效果之后会出现以焦虑和对毒品的强烈渴望为特征的烦躁不安状态。作为一种可能减轻这些负面后遗症的方法,50%至90%的可卡因使用者选择在可卡因狂欢期间同时使用乙醇。据报道,这种联合使用会延长“兴奋感”,并减少与使用可卡因相关的“低落感”。
当前的研究旨在评估这种现象是否可以在动物实验室中模拟。我们之前已经表明,在直道上奔跑以获取静脉注射可卡因奖励的动物会形成一种独特的趋近-回避“冲突”行为,其特征是当实验对象接近目标箱时会出现停止和后退行为。后退行为被认为反映了与目标箱同时存在的积极(奖励)和消极(焦虑)关联,并且可以通过地西泮预处理以剂量依赖的方式减少,这可能减轻了冲突引起的焦虑。
为了测试乙醇在减轻可卡因诱导的焦虑中的作用,训练大鼠在直臂通道中奔跑,以便每天单次静脉注射可卡因(1.0毫克/千克)。
在每天的跑道试验后有机会立即饮用8%或4%蔗糖-乙醇溶液的大鼠,与在注射可卡因后不饮用乙醇的大鼠相比,表现出的后退行为更少。
这些结果表明,乙醇有效地减少了在为静脉注射可卡因而在通道中奔跑的动物中趋近-回避冲突的发展,这一结果可能解释了人类中可卡因与乙醇联合使用的普遍性。