Chronic opioid exposure differentially modulates oxycodone self-administration in male and female rats.
Chronic opioid exposure differentially modulates oxycodone self-administration in male and female rats.
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DOI：
10.1111/adb.12973
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发表时间：
2021-05
影响因子：
3.4
通讯作者：
Chartoff E
中科院分区：
文献类型：
--
作者：
Mavrikaki M;Lintz T;Constantino N;Page S;Chartoff E
戒断阿片类止痛药可能会产生短暂的身体症状和长期的心理症状，包括焦虑和抑郁样状态，这通常会导致阿片类药物滥用和阿片类药物使用障碍 (OUD)。测试阿片类药物戒断会增强阿片类药物自我给药（SA）的增强作用这一假设的研究在很大程度上没有结论，并且主要集中在男性。尽管一些临床证据表明女性比男性更有可能滥用阿片类药物进行自我治疗，但缺乏针对两性的临床前研究。根据临床报告，我们假设，与雄性大鼠相比，停止注射渐增剂量的吗啡（近似于处方止痛药方案）会导致雌性大鼠羟考酮 SA 的增加程度更大。增加吗啡剂量（5-30 mg/kg 或赋形剂，每天两次，持续 12 天）后，大鼠经历为期 2 周的戒断期，在此期间测量戒断症状。评估了这种治疗对羟考酮 SA 获取、维持、剂量反应和渐进比率反应的影响，并进行了性别比较的额外分析。我们发现，两种性别都表现出躯体退缩，而只有雄性在温水甩尾试验中表现出痛觉过敏。在 SA 获得过程中，先前接触过吗啡的男性服用的羟考酮明显多于女性。最后，在渐进比例测试中，先前接触过吗啡的女性表现出对 SA 羟考酮的动机最低。与我们最初的假设相反，我们的研究结果表明，先前接触阿片类药物会增加男性更容易滥用，并降低羟考酮对女性的增强功效。剂量递增、非偶然的吗啡治疗会导致雄性和雌性大鼠产生依赖性。戒断经历增强了男性对羟考酮自我给药的获得，并减少了女性对羟考酮自我给药的维持。这些发现证明了生物性别对阿片类药物依赖和自愿摄入的影响，这将有助于指导对阿片类药物使用障碍中性别差异的机械理解。
Withdrawal from opioid painkillers can produce short‐lived physical symptoms and protracted psychological symptoms including anxiety and depressive‐like states that often lead to opioid misuse and opioid use disorder (OUD). Studies testing the hypothesis that opioid withdrawal potentiates the reinforcing effects of opioid self‐administration (SA) are largely inconclusive and have focused on males. Although some clinical evidence indicates that women are more likely than men to misuse opioids to self‐medicate, preclinical studies in both sexes are lacking. Based on clinical reports, we hypothesized that withdrawal from escalating‐dose morphine injections that approximates a prescription painkiller regimen would lead to increased oxycodone SA to a greater extent in female compared to male rats. After escalating‐dose morphine (5–30 mg/kg or vehicle, twice/day for 12 days), rats underwent a 2‐week abstinence period during which withdrawal signs were measured. The impact of this treatment was assessed on oxycodone SA acquisition, maintenance, dose response, and progressive ratio responding, with additional analyses to compare sexes. We found that both sexes expressed somatic withdrawal, whereas only males demonstrated hyperalgesia in the warm water tail flick assay. During SA acquisition, males with prior morphine exposure took significantly more oxycodone than females. Finally, females with prior morphine exposure demonstrated the lowest motivation to SA oxycodone in the progressive ratio test. Contrary to our initial hypothesis, our findings suggest that prior opioid exposure increases vulnerability to initiate misuse more in males and decreases the reinforcing efficacy of oxycodone in females. Escalating‐dose, noncontingent morphine treatment produces dependence in male and female rats. Withdrawal experience potentiates acquisition of oxycodone self‐administration in males and diminishes maintenance of oxycodone self‐administration in females. These findings demonstrate an impact of biological sex throughout opioid dependence and voluntary intake that will help guide mechanistic understanding of sex differences in opioid use disorder.
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影响因子：
3.7
作者：
Leknes S;Lee M;Berna C;Andersson J;Tracey I
通讯作者：
Tracey I
影响因子：
2.9
作者：
Enman, Nicole M.;Reyes, Beverly A. S.;Van Bockstaele, Elisabeth J.
通讯作者：
Van Bockstaele, Elisabeth J.
影响因子：
2.9
作者：
Kelley, AE;Bakshi, VP;Zhang, M
通讯作者：
Zhang, M
DOI：
10.1124/jpet.108.139196
发表时间：
2008-09-01
影响因子：
3.5
作者：
Cooper, Ziva D.;Truong, Yen Nhu-Thi;Woods, James H.
通讯作者：
Woods, James H.
影响因子：
4.7
作者：
ACQUAS, E;DICHIARA, G
通讯作者：
DICHIARA, G