Modeling cocaine relapse in rodents: Behavioral considerations and circuit mechanisms.
Modeling cocaine relapse in rodents: Behavioral considerations and circuit mechanisms.
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DOI：
10.1016/j.pnpbp.2018.01.002
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发表时间：
2018-12-20
影响因子：
5.6
通讯作者：
Mahler SV
中科院分区：
文献类型：
--
作者：
Farrell MR;Schoch H;Mahler SV
成瘾是一种慢性复发性疾病，因为大多数选择戒毒的成瘾者无法长期保持戒断状态。当康复中的成瘾者遇到诸如少量“引发”剂量的毒品、压力或与毒品相关的线索和地点等风险因素时，复发的可能性尤其大。在啮齿动物中，这些相同的因素会在一段戒断期后恢复对可卡因的寻求，大量的临床前研究利用引发、压力或线索恢复模型来揭示可卡因恢复背后的脑回路。在此，我们回顾了常见的可卡因复发大鼠模型，并讨论了每个模型的特定特征如何影响在恢复的药物寻求过程中所募集的神经回路。为了说明这一点，我们强调了腹侧苍白球亚回路在由可卡因相关线索或可卡因本身所恢复的可卡因寻求中所起的令人惊讶的特定作用。此类研究的一个目标是识别并最终逆转某些人无法控制其药物使用的潜在特定回路活动。基于临床前研究结果，我们假定人类的回路活动也因引发渴望和复发的触发因素而有所不同，并且相关的神经反应可能有助于预测在特定个体中最有可能引发复发的触发因素。如果是这样，检查回路活动可以促进对成瘾人群亚组的诊断，从而根据最成问题的风险因素进行个体化治疗。
Addiction is a chronic relapsing disorder, in that most addicted individuals who choose to quit taking drugs fail to maintain abstinence in the long-term. Relapse is especially likely when recovering addicts encounter risk factors like small “priming” doses of drug, stress, or drug-associated cues and locations. In rodents, these same factors reinstate cocaine seeking after a period of abstinence, and extensive preclinical work has used priming, stress, or cue reinstatement models to uncover brain circuits underlying cocaine reinstatement. Here, we review common rat models of cocaine relapse, and discuss how specific features of each model influence the neural circuits recruited during reinstated drug seeking. To illustrate this point, we highlight the surprisingly specific roles played by ventral pallidum subcircuits in cocaine seeking reinstated by either cocaine-associated cues, or cocaine itself. One goal of such studies is to identify, and eventually to reverse the specific circuit activity that underlies the inability of some humans to control their drug use. Based on preclinical findings, we posit that circuit activity in humans also differs based on the triggers that precipitate craving and relapse, and that associated neural responses could help predict the triggers most likely to elicit relapse in a given person. If so, examining circuit activity could facilitate diagnosis of subgroups of addicted people, allowing individualized treatment based on the most problematic risk factors.
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