Female and male rats readily consume and prefer oxycodone to water in a chronic, continuous access, two-bottle oral voluntary paradigm.
Female and male rats readily consume and prefer oxycodone to water in a chronic, continuous access, two-bottle oral voluntary paradigm.
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在长期、连续、两瓶口服自愿模式中，雌性和雄性大鼠很容易消耗并更喜欢羟考酮而不是水。
DOI：
10.1016/j.neuropharm.2020.107978
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发表时间：
2020
影响因子：
4.7
通讯作者：
Eisch,AmeliaJ
中科院分区：
文献类型：
--
作者：
Zanni,Giulia;DeSalle,MatthewJ;Deutsch,HannahM;Barr,GordonA;Eisch,AmeliaJ
阿片类药物--如羟考酮--的滥用日益增多，给卫生和社会经济系统带来了重大挑战。人类处方阿片类药物滥用的特点是慢性、自愿、口服摄入量和性别差异。为了开发干预措施，该领域将受益于临床前范例，该范例类似地为啮齿动物提供长期、持续、口服、自愿和自由选择的羟考酮。在这里，我们展示了雌性和雄性大鼠自愿摄入和选择羟考酮而不是水，并显示了在长期口服自愿、两瓶选择、连续获取范式中服用羟考酮的依赖性和动机。成年雌性和雄性Long-Evans大鼠被给予无限制、连续的回家机会，获得两个装水的瓶子(对照组)或一瓶水和一瓶溶于水的羟考酮(实验)。几乎所有的实验大鼠都自愿饮用羟考酮(~10 mg/kg/天)，并在22周内增加了摄入量。女性自己服用的羟考酮按体重计算是男性的两倍(导致血液中的羟考酮水平更高)，并且与男性相比，她们会更多地啃咬木块。急促戒断表明，男女都有很高的依赖程度。反映了饮用羟考酮的动机，柠檬酸浓度的上升抑制了羟考酮的摄入量(试验组)和水的摄入量(对照组)；然而，试验组大鼠恢复到柠檬酸前的偏好水平，而对照组大鼠没有。大鼠在野外探险的预筛选行为可以预测羟考酮的摄入量。因此，在这个慢性的两瓶口服选择范例中，大鼠随着时间的推移摄入和偏爱羟考酮，并且两性都表现出许多人类滥用羟考酮的特征。
The increasing abuse of opioids - such as oxycodone - poses major challenges for health and socioeconomic systems. Human prescription opioid abuse is marked by chronic, voluntary, oral intake and sex differences. To develop interventions, the field would benefit from a preclinical paradigm that similarly provides rodents with chronic, continuous, oral, voluntary and free-choice access to oxycodone. Here we show female and male rats voluntarily ingest and choose oxycodone over water and show both dependence and motivation to take oxycodone during a chronic oral voluntary, two-bottle choice, continuous access paradigm. Adult female and male Long-Evans rats were given unlimited, continuous homecage access to two bottles containing water (Control) or one bottle of water and one bottle of oxycodone dissolved in water (Experimental). Virtually all experimental rats voluntarily drank oxycodone (~10 mg/kg/day) and escalated their intake over 22 weeks. Females self-administered twice as much oxycodone by body weight (leading to higher blood levels of oxycodone) and engaged in more gnawing behavior of wooden blocks relative to males. Precipitated withdrawal revealed high levels of dependence in both sexes. Reflecting motivation to drink oxycodone, ascending concentrations of citric acid suppressed the intake of oxycodone (Experimental) and the intake of water (Control); however, Experimental rats returned to pre-citric acid preference levels whereas Controls rats did not. Pre-screening behaviors of rats on open field exploration predicted oxycodone intake. Thus, rats consumed and preferred oxycodone over time in this chronic two-bottle oral choice paradigm and both sexes displayed many features of human oxycodone abuse.