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Exploring the interoceptive stimulus effects of nicotine and varenicline

机译：探索尼古丁和瓦尼尼线的间歇性刺激作用

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摘要

Learning processes associated with nicotine influence the development of addiction to tobacco products. In the present report, we are interested in the interoceptive stimulus effects of nicotine acquiring control over appetitive behaviors - specifically, reward seeking. Also of interest is the current smoking cessation drug, varenicline (Chantix((R))). Varenicline, with its nicotine-like stimulus effects, can decrease withdrawal and cravings for a subset of individuals addicted to nicotine, though relapse is still common. We trained rats (N = 48) with nicotine (0.4 mg/kg, SC) as an excitatory stimulus (i.e., paired with sucrose) in a drug-discriminated goal-tracking (DGT) task. There was no access to sucrose on interspersed saline days. After acquisition of the initial nicotine-saline discrimination, rats were separated into four groups to test discrimination reversal and drug substitution. The control group maintained nicotine as the excitatory stimulus (NIC +). The substitution group had varenicline (1 mg/kg) replace nicotine as the stimulus paired with sucrose (VAR +). One reversal group had nicotine signal the absence of sucrose (i.e., now available on intermixed saline sessions; NIC). The last group was similar to the NIC- group except varenicline replaced nicotine on non-reinforced sessions (VAR). We found that varenicline fully substituted as the training stimulus when the drug-sucrose relation remained in place (VAR +). Both reversal groups acquired the new discrimination, albeit slowly and more variable for the VAR - group in comparison to NIC. There was an effect of group during substitution testing. Specifically, nicotine fully substituted for varenicline regardless of condition. However, varenicline only partially substituted for the nicotine stimulus. At the start of extinction, responding mimicked that of the rats training condition. However, by extinction session 12, all groups maintained similarly low levels of responding. These findings show nicotine and varenicline share stimulus elements, yet the conclusion of partial to full substitution depends on the nature of the testing protocol.
机译：与尼古丁相关的学习过程会影响烟草产品成瘾的发展。在本报告中，我们对尼古丁获取控制对快餐行为的感染刺激作用感兴趣 - 具体而言，奖励寻求。兴趣的是目前的吸烟药物，varenicline（chantix（（r）））。随着尼古丁的刺激效果，varenicline可以减少沉迷于尼古丁的个体子集的戒断和渴望，但复发仍然很常见。在药物区分的目标跟踪（DGT）任务中，我们用尼古丁（0.4mg / kg，sc）用尼古丁（0.4mg / kg，sc）用尼古丁（0.4mg / kg，sc）作为兴奋性刺激（即，与蔗糖配对）。在穿插盐水日没有进入蔗糖。在获取初始尼古丁 - 盐水鉴别后，将大鼠分成四组，以测试识别逆转和药物取代。对照组维持尼古丁作为兴奋性刺激（NIC +）。替代组具有varenicline（1 mg / kg）替代尼古丁作为用蔗糖（var +）配对的刺激。一个逆转组含有尼古丁信号，不存在蔗糖（即，现在可在混合的盐水会上使用; NIC）。最后一组与NIC组相似，除了在非加强会话上取代尼古丁（VAR）。我们发现当药物 - 蔗糖关系保持在适当的时（var +）时，varenicline完全被替代为训练刺激。与NIC相比，逆转群体均获得了var - 组的缓慢和更多变量。替代测试期间，组有效果。具体而言，无论条件如何，尼古丁完全取代瓦尼尼线。然而，varenicline仅部分取代尼古丁刺激。在灭绝开始时，响应模仿大鼠训练状况。然而，通过灭绝会话12，所有组保持同样低的响应程度。这些研究结果显示尼古丁和瓦尼尼线股刺激元件，但部分到全替代的结论取决于测试方案的性质。

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