Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine-conditioned place preference and associated changes in AMPA receptor binding.
Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine-conditioned place preference and associated changes in AMPA receptor binding.
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DOI：
10.1111/adb.12624
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发表时间：
2019-07
影响因子：
3.4
通讯作者：
Wonnacott S
中科院分区：
文献类型：
--
作者：
Wright VL;Georgiou P;Bailey A;Heal DJ;Bailey CP;Wonnacott S
复发是阿片类药物成瘾治疗中的一个主要问题。巴甫洛夫条件反射在反复复发中起作用，暴露于药物摄入过程中学到的线索可以促使药物服用复发。α7烟碱乙酰胆碱受体（nAChR）与认知的注意力方面以及学习和记忆的机制有关。在这项研究中，我们研究了α7 nAChRs在吗啡条件性位置偏爱（morphine-CPP）中的作用。CPP提供了一种与药物依赖的联想方面有关的联想学习模型。α7 nAChR拮抗剂甲基乌头碱（MLA; 4 mg/kg s.c.）在小鼠和大鼠中，对吗啡-CPP的获得、维持、再巩固或消退没有影响，但选择性地减弱了吗啡引发的CPP恢复。小鼠中吗啡-CPP的恢复伴随着腹侧海马中[3 H]-AMPA结合（但不是[3 H]-MK 801结合）的选择性增加，这是通过MLA的预先处理预防的。在全身性吗啡引发剂量之前，将MLA（6.7 μg）直接给予大鼠腹侧海马，可消除吗啡-CPP的恢复，而将MLA递送至背侧海马或前额叶皮质则无影响。这些结果表明，腹侧海马中的α7 nAChR在消退期后的关联药物记忆的恢复中发挥特定作用，使其成为预防复发的潜在靶点。
Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine‐conditioned place preference (morphine‐CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence. The α7 nAChR antagonist methyllycaconitine (MLA; 4 mg/kg s.c.) had no effect on the acquisition, maintenance, reconsolidation or extinction of morphine‐CPP but selectively attenuated morphine‐primed reinstatement of CPP, in both mice and rats. Reinstatement of morphine‐CPP in mice was accompanied by a selective increase in [3H]‐AMPA binding (but not in [3H]‐MK801 binding) in the ventral hippocampus that was prevented by prior treatment with MLA. Administration of MLA (6.7 μg) directly into the ventral hippocampus of rats prior to a systemic priming dose of morphine abolished reinstatement of morphine‐CPP, whereas MLA delivered into the dorsal hippocampus or prefrontal cortex was without effect. These results suggest that α7 nAChRs in the ventral hippocampus play a specific role in the retrieval of associative drug memories following a period of extinction, making them potential targets for the prevention of relapse.
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DOI：
10.1017/s1461145713000874
发表时间：
2014-01-01
影响因子：
4.8
作者：
Liu, Xiu
通讯作者：
Liu, Xiu
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
2.9
作者：
Duncan, GE;Miyamoto, S;Snouwaert, JN
通讯作者：
Snouwaert, JN
影响因子：
3.5
作者：
Bloem B;Poorthuis RB;Mansvelder HD
通讯作者：
Mansvelder HD
影响因子：
7.3
作者：
Kilkenny, Carol;Browne, William;Altman, Douglas G.
通讯作者：
Altman, Douglas G.