Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Pharmacol Biochem Behav. 2019 Jun;181:9-16. doi: 10.1016/j.pbb.2019.04.001. Epub 2019 Apr 4.
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®). 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.
与尼古丁相关的学习过程会影响到对烟草产品的成瘾。在本报告中，我们感兴趣的是尼古丁的内感受性刺激效应对食欲行为的控制作用，特别是对奖励寻求的控制作用。另一个感兴趣的是目前的戒烟药物伐伦克林（Chantix®）。伐伦克林具有类似尼古丁的刺激作用，可以减少一部分尼古丁成瘾者的戒断症状和对尼古丁的渴望，但仍会经常复发。我们用尼古丁（0.4mg/kg，SC）作为兴奋性刺激物（即与蔗糖配对），对大鼠（N=48）进行了药物辨别目标跟踪（DGT）任务训练。在混合的盐水日没有蔗糖供应。在初步获得尼古丁-盐水辨别后，将大鼠分为四组进行辨别反转和药物替代测试。对照组保持尼古丁作为兴奋性刺激物（NIC+）。替代组用伐伦克林（1mg/kg）替代与蔗糖配对的尼古丁（VAR+）。一个反转组让尼古丁表示蔗糖不再可用（即在混合的盐水日中可用；NIC-）。最后一组与 NIC-组相似，只是在非强化日中用伐伦克林替代尼古丁（VAR-）。我们发现，当药物-蔗糖关系保持不变时，伐伦克林完全替代了训练刺激物（VAR+）。两个反转组都获得了新的辨别能力，尽管 VAR-组的速度较慢，而且变化较大。在替代测试中存在组间效应。具体来说，无论条件如何，尼古丁都完全替代了伐伦克林。然而，伐伦克林只能部分替代尼古丁刺激。在消退的开始阶段，反应模式与训练条件下的大鼠相似。然而，到了第 12 次消退测试时，所有组的反应都保持在相似的低水平。这些发现表明，尼古丁和伐伦克林具有共同的刺激元素，但完全替代或部分替代的结论取决于测试方案的性质。
