Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use.
Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use.
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DOI：
10.1007/s00213-022-06134-4
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发表时间：
2022-08
影响因子：
3.4
通讯作者：
Kantak KM
中科院分区：
文献类型：
--
作者：
Mathieson E;Irving C;Koberna S;Nicholson M;Otto MW;Kantak KM
对海洛因+可卡因多物质使用的不良后果不敏感的性质和预测因素尚未很好地表征。结合严格控制的自我给药动物模型和抑制控制和回避行为措施的翻译方法可能有助于澄清这一问题。区分预先存在的抑制控制缺陷与药物使用史对不良后果不敏感的潜在贡献的关键方法是比较两种大鼠菌株：Wistar (WIS/Crl)，一种近交系，和自发性高血压大鼠（SHR/NCrl），一种近交系，先前显示相对于WIS/Crl，可卡因和海洛因的自我给药增加，抑制控制差。在单独的任务中，SHR/NCrl比WIS/Crl在药物暴露前表现出更大的冲动行为和强迫行为。在两种不同给药时间表下，SHR/NCrl自我给药量大于WIS/Crl，但自我给药量与WIS/Crl相似。当一半的会话周期受到随机足部电击的惩罚时，自我服用可卡因时，SHR/NCrl最初对惩罚的敏感度低于WIS/Crl，但在自我服用海洛因+可卡因时，他们对惩罚的敏感度相似。基于相关分析，只有特质冲动性预测了自我服用可卡因和接受生理盐水的大鼠的回避能力。而自用海洛因+可卡因大鼠的回避能力仅与药物使用量有关。此外，基线药物寻找和服用预测了自我施用可卡因或海洛因+可卡因的大鼠的惩罚敏感性。基于该动物模型的发现，人类实验室研究海洛因和可卡因多物质使用者与单一物质使用者对不良后果不敏感的性质和预测因素是有必要的。在线版本包含补充材料，可在10.1007/s00213-022-06134-4获得。
The nature and predictors of insensitivity to aversive consequences of heroin + cocaine polysubstance use are not well characterized. Translational methods incorporating a tightly controlled animal model of drug self-administration and measures of inhibitory control and avoidance behavior might be helpful for clarifying this issue. The key approach for distinguishing potential contributions of pre-existing inhibitory control deficits vs. drug use history in meditating insensitivity to aversive consequences was comparison of two rat strains: Wistar (WIS/Crl), an outbred strain, and the spontaneously hypertensive rat (SHR/NCrl), an inbred strain shown previously to exhibit heightened cocaine and heroin self-administration and poor inhibitory control relative to WIS/Crl. In separate tasks, SHR/NCrl displayed greater impulsive action and compulsive-like behavior than WIS/Crl prior to drug exposure. Under two different schedules of drug delivery, SHR/NCrl self-administered more cocaine than WIS/Crl, but self-administered a similar amount of heroin + cocaine as WIS/Crl. When half the session cycles were punished by random foot shock, SHR/NCrl initially were less sensitive to punishment than WIS/Crl when self-administering cocaine, but were similarly insensitive to punishment when self-administering heroin + cocaine. Based on correlation analyses, only trait impulsivity predicted avoidance capacity in rats self-administering cocaine and receiving yoked-saline. In contrast, only amount of drug use predicted avoidance capacity in rats self-administering heroin + cocaine. Additionally, baseline drug seeking and taking predicted punishment insensitivity in rats self-administering cocaine or heroin + cocaine. Based on the findings revealed in this animal model, human laboratory research concerning the nature and predictors of insensitivity to aversive consequences in heroin and cocaine polysubstance vs. monosubstance users is warranted. The online version contains supplementary material available at 10.1007/s00213-022-06134-4.
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影响因子：
2.7
作者：
Harvey, Roxann C.;Jordan, Chloe J.;Tassin, David H.;Moody, Kayla R.;Dwoskin, Linda P.;Kantak, Kathleen M.
通讯作者：
Kantak, Kathleen M.
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