Ranking the contribution of behavioral measures comprising oxycodone self-administration to reinstatement of drug-seeking in male and female rats.
Ranking the contribution of behavioral measures comprising oxycodone self-administration to reinstatement of drug-seeking in male and female rats.
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DOI：
10.3389/fnbeh.2022.1035350
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发表时间：
2022
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
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戒断期间药物使用的复发率是阿片类药物使用障碍（OUD）中最高的。在临床前研究中，重新寻求药物已经被广泛研究作为复发的模型，但这项工作主要是在男性身上进行的。我们询问生理性别是否对大鼠自我服用处方阿片类药物羟考酮的行为有影响，并计算了这些行为措施对雄性和雌性大鼠恢复的相对贡献。大鼠被训练自我给药羟考酮（8天，训练期），之后我们在另外14天的时间里观察雄性和雌性大鼠的自我给药行为：短时间给药（ShA， 1小时/天）、长时间给药（LgA， 6小时/天）和生理盐水自我给药。在14 d的强制戒断期后，对所有大鼠进行线索诱导的药物寻找恢复测试。我们量化了注射次数、药物摄入的前负荷、非强化杠杆按压、注射间隔、摄入的增加和主动杠杆上的恢复反应。在LgA和ShA条件下，雄性和雌性大鼠的羟考酮摄入量增加的程度相似。然而，在LgA条件下，男性的非强化反应水平高于女性，女性的恢复反应水平高于男性。然后，我们将上面列出的每个与成瘾相关的措施与男性和女性的恢复反应联系起来，并对它们各自的相对贡献进行排名。虽然大多数与羟考酮自我给药相关的行为测量本身并没有表现出性别差异，但当使用偏最小二乘回归分析时，它们对恢复的相对贡献是性别依赖的。经计算，在两性中，前负荷行为对恢复的相对贡献最高，长间隔和短间隔对恢复的贡献分别在雌性和雄性中位居第二。我们的研究结果显示了一些羟考酮自我给药措施的性别差异。更重要的是，我们证明了性别依赖的自我管理行为可以预测恢复的程度，这对预防复发有很大的希望。
Rates of relapse to drug use during abstinence are among the highest for opioid use disorder (OUD). In preclinical studies, reinstatement to drug-seeking has been extensively studied as a model of relapse–but the work has been primarily in males. We asked whether biological sex contributes to behaviors comprising self-administration of the prescription opioid oxycodone in rats, and we calculated the relative contribution of these behavioral measures to reinstatement in male and female rats. Rats were trained to self-administer oxycodone (8 days, training phase), after which we examined oxycodone self-administration behaviors for an additional 14 days under three conditions in male and female rats: short access (ShA, 1 h/d), long access (LgA, 6 h/d), and saline self-administration. All rats were then tested for cue-induced reinstatement of drug-seeking after a 14-d forced abstinence period. We quantified the # of infusions, front-loading of drug intake, non-reinforced lever pressing, inter-infusion intervals, escalation of intake, and reinstatement responding on the active lever. Both male and female rats in LgA and ShA conditions escalated oxycodone intake to a similar extent. However, males had higher levels of non-reinforced responding than females under LgA conditions, and females had greater levels of reinstatement responding than males. We then correlated each addiction-related measure listed above with reinstatement responding in males and females and ranked their respective relative contributions. Although the majority of behavioral measures associated with oxycodone self-administration did not show sex differences on their own, when analyzed together using partial least squares regression, their relative contributions to reinstatement were sex-dependent. Front-loading behavior was calculated to have the highest relative contribution to reinstatement in both sexes, with long and short inter-infusion intervals having the second greatest contribution in females and males, respectively. Our results demonstrate sex differences in some oxycodone self-administration measures. More importantly, we demonstrate that a sex- dependent constellation of self-administration behaviors can predict the magnitude of reinstatement, which holds great promise for relapse prevention in people.
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DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
4.8
作者：
Mavrikaki, Maria;Anastasiadou, Eleni;Chartoff, Elena H.
通讯作者：
Chartoff, Elena H.
影响因子：
14.8
作者：
Carlezon, William A., Jr.;Chartoff, Elena H.
通讯作者：
Chartoff, Elena H.
影响因子：
3.4
作者：
Ahmed, SH;Koob, GF
通讯作者：
Koob, GF
影响因子：
3.4
作者：
Bakhti-Suroosh A;Towers EB;Lynch WJ
通讯作者：
Lynch WJ