Potentiation of cue-induced reinstatement of cocaine-seeking in rats by the anxiogenic drug yohimbine
Potentiation of cue-induced reinstatement of cocaine-seeking in rats by the anxiogenic drug yohimbine
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DOI：
10.1016/j.bbr.2006.06.039
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发表时间：
2006-11-01
影响因子：
2.7
通讯作者：
See, Ronald E.
中科院分区：
文献类型：
--
作者：
Feltenstein, Matthew W.;See, Ronald E.
压力和药物相关的线索可以触发戒毒可卡因使用者的药物欲望和复发。虽然这两个因素在复发中的作用是有据可查的，但尚不清楚压力和药物相关线索之间的相互作用是否会导致可卡因寻求行为的增强。在此，我们评估了在存在或不存在可卡因相关线索的情况下，致焦虑α（2）-去甲肾上腺素能受体拮抗剂育亨宾对大鼠可卡因寻求恢复的影响。育亨宾预处理在可卡因相关线索或线索本身的情况下可靠地恢复对先前可卡因配对杠杆的反应（比消光水平高3-4倍）。然而，如果育亨宾在提示诱导的恢复之前，动物表现出极大的增强反应（比灭绝水平高10-13倍，或比单独的提示或育亨宾高3-5倍）。虽然可卡因自我管理产生了显着增加血浆皮质酮，血浆皮质酮水平并没有表现出明确的关系，可卡因配对杠杆反应在线索和/或育亨宾诱导的恢复。这些结果表明，在压力状态下暴露于药物配对线索可以大大增强可卡因寻求，并建议未来的治疗干预措施应针对多种方式。(c)2006 Elsevier B. V.保留所有权利。
Stress and drug-associated cues can trigger drug desire and relapse in abstinent cocaine users. Although the role of these two factors in relapse is well documented, it remains unclear as to whether an interaction between stress and drug-associated cues can lead to an enhancement in cocaine-seeking behavior. Here, we assessed the effects of the anxiogenic alpha(2)-noradrenergic receptor antagonist, yohimbine, on reinstatement of cocaine-seeking in rats either in the presence or absence of cocaine-associated cues. Yohimbine pretreatment in the absence of cocaine-associated cues or cues by themselves reliably reinstated responding on the previously cocaine-paired lever (3-4 times higher than extinction levels). However, animals showed greatly potentiated responding if yohimbine preceded cue-induced reinstatement (10-13 times higher than extinction levels, or 3-5 times over cues or yohimbine alone). While cocaine self-administration produced a significant increase in plasma corticosterone, plasma corticosterone levels did not show a clear relationship to cocaine-paired lever responding during cue and/or yohimbine-induced reinstatement. These results demonstrate that exposure to drug-paired cues during a stressful state can greatly potentiate cocaine-seeking and suggest that future treatment interventions should target multiple modalities. (c) 2006 Elsevier B.V. All rights reserved.