Cue-induced reinstatement of cocaine seeking in the rat "conflict model": Effect of prolonged home-cage confinement

Cue-induced reinstatement of cocaine seeking in the rat "conflict model": Effect of prolonged home-cage confinement
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DOI:
10.1007/s00213-011-2416-z
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发表时间:
2012-02-01
期刊:
影响因子:
3.4
通讯作者:
Zangen, Abraham
Zangen, Abraham
中科院分区:
医学3区
文献类型:
--
作者:
Barnea-Ygael, Noam;Yadid, Gal;Zangen, Abraham

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药物成瘾不仅仅是反复使用药物,还包括尽管对使用者产生了不良后果仍强迫性地使用药物。为了给实验动物引入寻求药物的不良后果,我们开发了“冲突模型”,在该模型中,大鼠要想触压能自行给药的强化杆,就必须穿过带电的网格地板。在这个模型中,可以单独测量导致完全停止寻求药物的电流强度。本研究旨在评估在存在电屏障的情况下,通过呈现与奖励相关的离散线索,是否能够恢复对药物或自然奖励的寻求,以及长时间的笼内限制是否能促进该模型中的这种恢复。“冲突模型”用于在笼内限制1天或14天后,在存在电屏障的情况下测试线索诱导的恢复情况,实验对象是先前经过训练可自行使用可卡因或蔗糖的大鼠组。尽管抑制蔗糖或可卡因自行给药所需的电击强度相似,但在恢复测试期间,与可卡因相关线索相比,实验对象对蔗糖相关线索的反应明显较低。重要的是,在笼内限制14天后,线索诱导的可卡因寻求恢复减弱。在自行给药模型中纳入厌恶后果能够检测到可被解释为药物强化物所特有的强迫性成分。此外,厌恶后果的影响似乎在笼内限制后增强。
Drug addiction is not just the repeated administration of drugs, but compulsive drug use maintained despite the accumulation of adverse consequences for the user. In an attempt to introduce adverse consequences of drug seeking to laboratory animals, we have developed the "conflict model," in which the access of rats to a reinforcing lever allowing self-administration requires passing of an electrified grid floor. In this model, the current intensity leading to complete abstinence from drug seeking can be measured individually. The present study was designed to evaluated whether reinstatement of drug or natural reward seeking, despite the presence of the electrical barrier, can be achieved by presentation of discrete cues that were associated with the reward, and whether prolonged home-cage confinement can facilitate such reinstatement in this model.The "conflict model" was used to test cue-induced reinstatement in the presence of the electrical barrier, after 1 or 14 days of home-cage confinement, in groups of rats that were previously trained to self-administer cocaine or sucrose.Although similar shock intensity was required to suppress sucrose or cocaine self-administration, subjects exhibited significantly lower response to sucrose-associated as compared to cocaine-associated cues, during the reinstatement test. Importantly, cue-induced reinstatement of cocaine seeking was attenuated following 14 days of home-cage confinement.The incorporation of aversive consequence in the self-administration model enable detection of what can be interpreted as a compulsive component unique to drug reinforcers. Moreover, the effect of the aversive consequence seems to increase following home-cage confinement.