在初次接触阿片类药物戒断期间，快感缺失程度越高，对随后的大鼠阿片类药物自我给药行为越具有保护作用。
Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.
机构信息
Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN, 55415, USA.
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
出版信息
Psychopharmacology (Berl). 2020 Aug;237(8):2279-2291. doi: 10.1007/s00213-020-05532-w. Epub 2020 May 9.
RATIONALE
Understanding 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 to withdrawal from initial drug exposure and later drug use vulnerability is unclear.
OBJECTIVE
The 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.
METHODS
Rats 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.
RESULTS
Greater 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.
CONCLUSIONS
Our 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.
原理
了解导致个体对阿片类药物成瘾易感性差异的因素对于开发更有效的预防和治疗方法至关重要，但在啮齿动物中，很少有可靠的行为预测因子可以预测随后的阿片类药物自我给药。对初始药物暴露的急性效应的敏感性可以预测人类和动物随后的成瘾易感性，但初始药物暴露戒断后敏感性与随后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戒断期间经历的快感缺失程度是否可以预测随后的阿片类药物自我给药易感性。
方法
首先，通过对吗啡（即“急性依赖”）的急性注射来测试大鼠的戒断敏感性，通过纳洛酮诱发和自发戒断期间颅内自我刺激（ICSS）阈值的升高来衡量（类快感缺失行为）。然后，通过各种静脉内吗啡自我给药（MSA）测量来测试大鼠的成瘾样行为，包括获得、需求、消退和由吗啡、应激和/或药物相关线索引起的复吸。
结果
在多次吗啡注射中，纳洛酮诱发的戒断程度越高，单次吗啡注射后自发性戒断的峰值越严重，与多次 MSA 测量中的成瘾样行为越低有关。与任何单一的 MSA 测量相比，戒断引起的快感缺失预测了更广泛的 MSA 测量范围。
结论
我们的数据将 WIA 确立为预测啮齿动物中阿片类药物 SA 个体差异的首批行为测量之一。该模型有望有助于进一步了解易感性脆弱性的行为和神经生物学机制对阿片类药物成瘾。
Zotero 插件