A buprenorphine-validated rat model of opioid use disorder optimized to study sex differences in vulnerability to relapse.
A buprenorphine-validated rat model of opioid use disorder optimized to study sex differences in vulnerability to relapse.
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DOI：
10.1007/s00213-020-05750-2
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发表时间：
2021-04
影响因子：
3.4
通讯作者：
Lynch WJ
中科院分区：
文献类型：
--
作者：
Bakhti-Suroosh A;Towers EB;Lynch WJ
阿片类药物使用障碍（OUD）是美国的一种主要流行病。尽管有证据表明 OUD 对女性可能特别严重，但临床前模型尚未将性别确定为 OUD 的主要因素。在这里，我们检查了间歇性芬太尼自我给药和长期戒断后复发易感性的性别差异，并使用丁丙诺啡（FDA 批准的 OUD 治疗方法）来测试我们模型的有效性。在两种训练条件之一下获得芬太尼自我给药后，雄性和雌性大鼠使用间歇性获取程序，每天 24 小时延长获取芬太尼（0.25 μg/kg/输注，10 天）。戒烟 14 天后，使用消退/提示诱导恢复程序评估复发的脆弱性；戒断期间服用丁丙诺啡（0 或 3 毫克/公斤/天）。长期自我服用芬太尼并戒断后，寻求药物的程度很高；丁丙诺啡显着减少了药物寻求，支持了我们的复发模型的有效性。女性自行注射了更多的芬太尼，并在随后的消退测试中产生了更高水平的反应。丁丙诺啡对男女均有效，并消除了寻求药物的性别和动情期差异。有趣的是，训练期间的暂停对女性后来的芬太尼自我给药产生了重大影响，但对男性没有影响，这表明最初的暴露条件会持续影响女性的脆弱性。这些发现证明了该大鼠模型在确定性别和激素对 OUD 发展和治疗的影响方面的实用性。
Opioid use disorder (OUD) is a major epidemic in the USA. Despite evidence indicating that OUD may be particularly severe for women, preclinical models have yet to establish sex as a major factor in OUD. Here, we examined sex differences in vulnerability to relapse following intermittent access fentanyl self-administration and protracted abstinence and used buprenorphine, the FDA-approved treatment for OUD, to test the validity of our model. Following acquisition of fentanyl self-administration under one of two training conditions, male and female rats were given extended, 24-h/day access to fentanyl (0.25 μg/kg/infusion, 10 days) using an intermittent access procedure. Vulnerability to relapse was assessed using an extinction/cue-induced reinstatement procedure following 14 days of abstinence; buprenorphine (0 or 3 mg/kg/day) was administered throughout abstinence. Levels of drug-seeking were high following extended-access fentanyl self-administration and abstinence; buprenorphine markedly decreased drug-seeking supporting the validity of our relapse model. Females self-administered more fentanyl and responded at higher levels during subsequent extinction testing. Buprenorphine was effective in both sexes and eliminated sex and estrous phase differences in drug-seeking. Interestingly, the inclusion of a time-out during training had a major impact on later fentanyl self-administration in females, but not males, indicating that the initial exposure conditions can persistently impact vulnerability in females. These findings demonstrate the utility of this rat model for determining sex and hormonal influences on the development and treatment of OUD.
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影响因子：
3.9
作者：
Fenn, Jennifer M.;Laurent, Jennifer S.;Sigmon, Stacey C.
通讯作者：
Sigmon, Stacey C.
影响因子：
3.4
作者：
Allain, Florence;Bouayad-Gervais, Karim;Samaha, Anne-Noel
通讯作者：
Samaha, Anne-Noel
影响因子：
2.7
作者：
ANGLIN, MD;HSER, YI;MCGLOTHLIN, WH
通讯作者：
MCGLOTHLIN, WH
影响因子：
10.6
作者：
Bossert, Jennifer M.;Kiyatkin, Eugene A.;Shaham, Yavin
通讯作者：
Shaham, Yavin
影响因子：
3.6
作者：
Cicero, TJ;Aylward, SC;Meyer, ER
通讯作者：
Meyer, ER