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可卡因及可卡因/海洛因组合在大鼠渐进比率和选择实验模式下强化作用的比较

Comparison of the reinforcing effects of cocaine and cocaine/heroin combinations under progressive ratio and choice schedules in rats.

作者信息

Ward Sara Jane, Morgan Drake, Roberts David C S

机构信息

Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

出版信息

Neuropsychopharmacology. 2005 Feb;30(2):286-95. doi: 10.1038/sj.npp.1300560.

Abstract

The co-use of cocaine and heroin is relatively common, with a growing clinical and preclinical literature dedicated to investigating the factors underlying the phenomenon. Specifically, several studies have compared the reinforcing effects of the coadministration of cocaine and heroin, referred to commonly as 'speedball', to either drug alone. The present study assessed whether addition of heroin to a wide range of cocaine doses produces reinforcing effects greater than cocaine alone using both a progressive ratio (PR) schedule and a choice procedure. Patterns of coadministration of cocaine and heroin offered simultaneously were also assessed using double-lumen cannulas. Under the PR schedule, speedball combinations across a range of doses (0.38-3.0 mg/kg/inf cocaine+1.5-48 microg/kg/inf heroin) did not support higher break points than cocaine alone. When cocaine and heroin were made available concurrently (ie on two separate levers), rats self-administered cocaine exclusively. Using a choice procedure, however, a preference was demonstrated for some speedball combinations (eg 0.18 mg/kg/inf cocaine+50 microg/kg/inf heroin; 0.38 mg/kg/inf cocaine+50 microg/kg/inf heroin) over cocaine alone (0.75 mg/kg/inf). So while results obtained using the PR schedule do not support the hypothesis that speedball combinations are more reinforcing than cocaine alone, data from the choice procedure do support this hypothesis. These apparently discrepant results demonstrate that these models are measuring different aspects of drug reinforcement, and suggest that choice procedures in rats provide a useful tool to study speedball self-administration.

摘要

可卡因和海洛因同时使用的情况较为常见,临床和临床前研究文献日益增多,致力于探究这一现象背后的因素。具体而言,多项研究比较了可卡因和海洛因联合使用(通常称为“速球”)与单独使用任一药物的强化效果。本研究使用累进比率(PR)程序和选择程序,评估在广泛的可卡因剂量中添加海洛因是否会产生比单独使用可卡因更强的强化效果。同时,还使用双腔插管评估了可卡因和海洛因同时给药的模式。在PR程序下,一系列剂量(0.38 - 3.0毫克/千克/注射可卡因 + 1.5 - 48微克/千克/注射海洛因)的速球组合并未产生比单独使用可卡因更高的断点。当可卡因和海洛因同时可用时(即在两个单独的杠杆上),大鼠只自行注射可卡因。然而,使用选择程序时,发现一些速球组合(例如0.18毫克/千克/注射可卡因 + 50微克/千克/注射海洛因;0.38毫克/千克/注射可卡因 + 50微克/千克/注射海洛因)比单独使用可卡因(0.75毫克/千克/注射)更受偏爱。因此,虽然使用PR程序获得的结果不支持速球组合比单独使用可卡因更具强化作用的假设,但选择程序的数据确实支持这一假设。这些明显矛盾的结果表明,这些模型测量的是药物强化的不同方面,并表明大鼠的选择程序为研究速球自我给药提供了一个有用的工具。

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