PDF(Pubmed)
Abstract：
Excessive prescribing and misuse of prescription opioids, such as oxycodone, significantly contributed to the current opioid crisis. Although oxycodone is typically consumed orally by humans, parenteral routes of administration have primarily been used in preclinical models of oxycodone dependence. To address this issue, more recent studies have used oral self-administration procedures to study oxycodone seeking and withdrawal in rodents. Behavioral differences, however, following oral oxycodone intake versus parenteral oxycodone administration remain unclear. Thus, the goal of the current studies was to compare anxiety- and withdrawal-like behaviors using established opioid dependence models of either home cage oral intake of oxycodone (0.5 mg/ml) or repeated subcutaneous (s.c.) injections of oxycodone (10 mg/kg) in male and female mice. Here, mice received 10 days of oral or s.c. oxycodone administration, and following 72 h of forced abstinence, anxiety- and withdrawal-like behaviors were measured using elevated zero maze, open field, and naloxone-induced precipitated withdrawal procedures. Global withdrawal scores were increased to a similar degree following oral and s.c. oxycodone use, while both routes of oxycodone administration had minimal effects on anxiety-like behaviors. When examining individual withdrawal-like behaviors, mice receiving s.c. oxycodone exhibited more paw tremors and jumps during naloxone-induced precipitated withdrawal compared with oral oxycodone mice. These results indicate that both models of oxycodone administration are sufficient to elevate global withdrawal scores, but, when compared with oral consumption, s.c. oxycodone injections yielded more pronounced effects on some withdrawal-like behaviors.
摘要：
过量处方和滥用处方阿片类药物，如羟考酮，严重助长了当前的阿片类药物危机。虽然羟考酮通常被人类口服，肠胃外给药途径主要用于羟考酮依赖的临床前模型。为了解决这个问题，最近的研究使用口服自我给药程序来研究啮齿动物的羟考酮寻求和戒断。行为差异,然而,口服羟考酮与肠胃外羟考酮治疗后的比较尚不清楚.因此，本研究的目的是使用已建立的阿片样物质依赖模型比较焦虑和戒断样行为,该模型包括家笼口服羟考酮(0.5mg/ml)或重复皮下(皮下)注射羟考酮(10mg/kg)。这里,小鼠接受10天口服或s.c.羟考酮给药，在强制禁欲72小时后，使用高架零迷宫测量焦虑和戒断样行为，开放领域，和纳洛酮诱导的沉淀戒断程序。口服和皮下使用羟考酮后，全球戒断得分增加到类似程度。而两种羟考酮给药途径对焦虑样行为的影响最小。当检查个体的类似退缩的行为时，与口服羟考酮小鼠相比，接受皮下羟考酮的小鼠在纳洛酮诱导的沉淀戒断期间表现出更多的爪震颤和跳跃。这些结果表明，两种羟考酮给药模式都足以提高全球戒断评分，但是,与口服相比，s.c.羟考酮注射对一些戒断样行为产生了更明显的影响。
