In the classical incubation of drug craving rat model, drug seeking is assessed after homecage forced abstinence. However, human abstinence is often voluntary because negative consequences of drug seeking outweigh the desire for the drug. Here, we developed a rat model of incubation of opioid craving after electric barrier-induced voluntary abstinence and determined whether the dopamine stabilizer (-)-OSU6162 would decrease this new form of incubation. We trained male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day) for 14 days. We then exposed them to either homecage forced abstinence or voluntary abstinence induced by an electric barrier of increasing intensity near the drug-paired lever. On abstinence days 1, 15, or 30, we tested the rats for oxycodone seeking without shock and drug. We also examined the effect of (-)-OSU6162 (7.5 and 15 mg/kg) on oxycodone seeking on abstinence day 1 or after 15 days of either voluntary or forced abstinence. Independent of sex, the time-dependent increase in oxycodone seeking after cessation of opioid self-administration (incubation of opioid craving) was stronger after voluntary abstinence than after forced abstinence. In males, (-)-OSU6162 decreased incubated (day 15) but not non-incubated (day 1) oxycodone seeking after either voluntary or forced abstinence. In females, (-)-OSU6162 modestly decreased incubated oxycodone seeking after voluntary but not forced abstinence. Results suggest that voluntary abstinence induced by negative consequences of drug seeking can paradoxically potentiate opioid craving and relapse. We propose the dopamine stabilizer (-)-OSU6162 may serve as an adjunct pharmacological treatment to prevent relapse in male opioid users.

中文翻译：

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多巴胺稳定剂（-）-OSU6162对电屏障诱导的自愿戒断后对阿片类药物渴望的潜伏培养的影响。

在对药物渴望大鼠模型的经典温育中，在强制笼养禁欲后评估药物寻找。但是，人类禁欲通常是自愿的，因为寻求毒品的负面后果超过了对毒品的渴望。在这里，我们建立了一个大鼠模型，该模型在电屏障诱导的自愿戒断后进行了阿片类药物渴望的培养，并确定了多巴胺稳定剂（-）-OSU6162是否会减少这种新的培养形式。我们训练了雄性和雌性大鼠自用羟考酮（0.1毫克/千克/输注，每天6小时），持续14天。然后，我们将他们暴露在因药物配对杠杆附近强度增加的电屏障引起的强制性禁食或自愿禁欲中。在禁欲日第1、15或30天，我们对大鼠进行了羟考酮的测试，未发现休克和药物。我们还检查了（-）-OSU6162（7.5和15 mg / kg）对在禁欲日第1天或自愿或强迫禁欲15天后寻求羟考酮的作用。与性别无关，自愿戒断后羟考酮在停止自用阿片类药物后（寻求阿片类药物的渴望）的时间依赖性增加比强迫戒断要强。在雄性中，（-）-OSU6162在寻求自愿戒除强迫戒毒后降低了温育（第15天）但未温育（第1天）的羟考酮水平。在雌性动物中，（-）-OSU6162适度降低了温育的羟考酮的使用率，但没有自愿戒断。结果表明，由寻求药物的负面后果引起的自愿戒酒可以自相矛盾地增强阿片类药物的渴望和复发。