The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse
The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse
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DOI：
10.1016/j.neuroscience.2007.10.012
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发表时间：
2008-01-24
期刊：
影响因子：
3.3
通讯作者：
See, R. E.
中科院分区：
文献类型：
--
作者：
Rogers, J. L.;Ghee, S.;See, R. E.
恢复已消失的药物寻求已被用于研究药物滥用，特别是可卡因复发的神经基质。然而，有限的研究已经检查了在条件提示或海洛因本身存在的情况下驱动海洛因寻求行为恢复的电路。为了验证一个假设，即有海洛因经验的动物恢复的电路会显示重叠，但与古柯有明显的不同！在海洛因配对线索或单次海洛因启动剂量产生的海洛因寻求恢复过程中，我们对一些皮质、纹状体和边缘脑区域进行了短暂抑制。在连续2周的时间里，大鼠在每天3小时的时间里，分别用条件刺激（CS）对海洛因进行杠杆按压，然后每天消除杠杆反应。在没有海洛因强化的情况下，用杠杆反应测量海洛因寻求的随后恢复。第一组恢复试验涉及双侧颅内输注GABA受体激动剂（巴氯芬-muscimol， B/M）或载体（生理盐水）到13个不同脑区之一后的反应性随机CS表现。第二组恢复试验涉及在B/M或车辆注射后单次注射海洛因（0.25 mg/kg, s.c）。我们的研究结果表明，注射了运载工具的动物恢复了CS呈现和海洛因启动注射，而已知对恢复可卡因寻求重要的几个区域的B/M失活也减弱了对CS呈现和/或海洛因启动剂量的海洛因的寻求。然而，正如预测的那样，先前显示不影响可卡因寻求的区域的失活显着减弱了海洛因寻求，这支持了海洛因寻求恢复背后的电路比可卡因更分散分布的假设。(c) 2008 IBRO。Elsevier Ltd.出版。版权所有。
Reinstatement of extinguished drug-seeking has been utilized in the study of the neural substrates of relapse to drugs of abuse, particularly cocaine. However, limited studies have examined the circuitry that drives the reinstatement of heroin-seeking behavior in the presence of conditioned cues, or by heroin itself. In order to test the hypothesis that the circuitry underlying reinstatement in heroin-experienced animals would show overlapping, yet distinct differences from coca! ne-experienced animals, we used transient inhibition of several cortical, striatal, and limbic brain regions during reinstatement of heroin-seeking produced by heroin-paired cues, or by a single priming dose of heroin. Rats lever pressed for i.v. heroin discretely paired with a conditioned stimulus (CS) during daily 3-h sessions for a period of 2 weeks, followed by daily extinction of lever responding. Subsequent reinstatement of heroin-seeking was measured as lever responding in the absence of heroin reinforcement. The first set of reinstatement tests involved response-contingent CS presentations following bilateral intracranial infusion of either a combination of GABA receptor agonists (baclofen-muscimol, B/M) or vehicle (saline) into one of 13 different brain regions. The second set of reinstatement tests involved a single heroin injection (0.25 mg/kg, s.c.) following either B/M or vehicle infusions. Our results showed that vehicle-infused animals reinstated to both CS presentations and a priming injection of heroin, while B/M inactivation of several areas known to be important for the reinstatement of cocaine-seeking also attenuated heroin-seeking in response to CS presentations and/or a priming dose of heroin. However, as predicted, inactivation of areas previously shown to not affect cocaine-seeking significantly attenuated heroin-seeking, supporting the hypothesis that the circuitry underlying the reinstatement of heroin-seeking is more diffusely distributed than that for cocaine. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.