Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.
Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.
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在大鼠中，从最初的阿片类药物暴露戒断期间较高的快感缺乏可以防止随后的阿片类药物自我给药。
DOI：
10.1007/s00213-020-05532-w
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发表时间：
2020
影响因子：
3.4
通讯作者：
Harris,AndrewC
中科院分区：
文献类型：
--
作者：
Swain,Yayi;Muelken,Peter;Skansberg,Annika;Lanzdorf,Danielle;Haave,Zachary;LeSage,MarkG;Gewirtz,JonathanC;Harris,AndrewC
合理了解导致个体对阿片成瘾易感性差异的因素对于开发更有效的预防和治疗至关重要，但在啮齿动物中发现了随后阿片类药物自我给药的可靠行为预测因子。在人类和动物中，对最初药物暴露的急性效应的敏感性预示着后来的成瘾易感性，但对最初药物暴露的敏感性与后来的药物使用易感性之间的关系尚不清楚。目的本研究的目的是评估在早期阿片类药物暴露期间经历的快感缺乏程度是否预测随后的阿片类药物自我给药的易感性。方法首先测试大鼠在急性注射吗啡后的戒断敏感性(即“急性依赖”)，测量在纳洛酮沉淀和自发戒断期间颅内自我刺激(ICSS)阈值(类快感行为)的升高。然后，使用不同的静脉注射方法测试大鼠的成瘾行为。吗啡自我给药(MSA)包括由吗啡、应激和/或药物相关线索诱导的获得、需求、消退和恢复。结果重复注射吗啡后纳洛酮催促戒断程度越高，单次注射吗啡后自发戒断峰值越严重，在多个MSA测量中，成瘾性行为越低。戒断诱导性快感缺乏症预测的MSA措施范围比任何单独的MSA措施本身都要大。结论我们的数据建立了WIA作为预测啮齿动物阿片类药物SA个体差异的首批行为指标之一。这一模型有望有助于我们进一步了解阿片成瘾易感性的行为和神经生物学机制。
RationaleUnderstanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship between sensitivity towithdrawalfrom initial drug exposure and later drug use vulnerability is unclear.ObjectiveThe goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid self-administration.MethodsRats were first tested for withdrawal sensitivity following acute injections of morphine (i.e., “acute dependence”), measured as elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during naloxone-precipitated and spontaneous withdrawal. Rats were then tested for addiction-like behavior using various measures of i.v. morphine self-administration (MSA) including acquisition, demand, extinction, and reinstatement induced by morphine, stress, and/or drug-associated cues.ResultsGreater naloxone-precipitated withdrawal across repeated morphine injections and greater peak spontaneous withdrawal severity following a single morphine injection were associated with lower addiction-like behavior on multiple MSA measures. Withdrawal-induced anhedonia predicted a wider range of MSA measures than did any individual measure of MSA itself.ConclusionsOur data establish WIA as one of the first behavioral measures to predict individual differences in opioid SA in rodents. This model promises to be useful for furthering our understanding of behavioral and neurobiological mechanisms underlying vulnerability to opioid addiction.