Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.
Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.
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DOI：
10.1037/pha0000375
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发表时间：
2021-12
影响因子：
2.3
通讯作者：
Hossain A
中科院分区：
文献类型：
--
作者：
Gipson CD;Dunn KE;Bull A;Ulangkaya H;Hossain A
阿片类药物使用障碍 (OUD) 是一个重大的健康问题，了解 OUD 各个方面（包括药物使用和戒断）的机制非常重要。临床前模型为评估阿片类药物戒断机制提供了理想的机会。目前的模型受到以下限制：依赖强制阿片类药物给药、关注急性（而非长期）综合征以及排除女性。在这项研究中，测量了雄性和雌性大鼠自行注射海洛因（维持剂量为 12.5 μg/kg/输注）后突然停药后的阿片类药物戒断情况。在第一阶段，在最后一次自我给药后0、16、48和72小时对雄性和雌性大鼠的急性戒断症状进行评估。总躯体症状增加直至 48 小时（主要是女性），海洛因摄入量与 48 小时和 72 小时时间点的总躯体症状呈正相关。多动症和焦虑样行为的测量值分别增加 16 小时和 48 小时。在第 2 阶段，在第 1 阶段的一组雄性和雌性大鼠中，在基线、急性和长期（自我给药后 168 和 312 小时）时间点评估症状。不同时间点的躯体体征总数没有差异，但与雄性相比，雌性在所有时间点都表现出明显更高的体温，表明性别特异性的长期戒断症状。这些数据提供了啮齿动物自我给药和突然停药后阿片类药物戒断症状的全面表征，为未来旨在模拟人类经历的研究奠定了基础，并证明了在阿片类药物自我给药临床前模型中以性别特异性表征急性和长期戒断的重要性。
Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) opioid withdrawal following abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hrs following the last self-administration session. Total somatic signs increased until 48 hrs (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hrs, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hrs after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared to males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology following self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration.
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影响因子：
10.6
作者：
Heilbronner SR;Rodriguez-Romaguera J;Quirk GJ;Groenewegen HJ;Haber SN
通讯作者：
Haber SN
影响因子：
4.2
作者：
Lewis, Ben;Hoffman, Lauren A.;Nixon, Sara Jo
通讯作者：
Nixon, Sara Jo
影响因子：
6.1
作者：
COX, B;ARY, M;LOMAX, P
通讯作者：
LOMAX, P
影响因子：
3.5
作者：
Franklin, Teresa R.;Ehrman, Ronald;Childress, Anna Rose
通讯作者：
Childress, Anna Rose
影响因子：
3.4
作者：
Fuchs, RA;See, RE
通讯作者：
See, RE