Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Pharmacol Biochem Behav. 2020 Dec;199:173045. doi: 10.1016/j.pbb.2020.173045. Epub 2020 Oct 12.
Nicotine and varenicline (Chantix®; the leading non-nicotine cessation pharmacotherapy) can come to control appetitive behaviors such as goal-tracking. We tested rats (N = 48) in a drug-discriminated goal-tracking (DGT) task where each rat received daily subcutaneous injections of either nicotine (0.4 mg/kg) or saline (0.9% [w/v]) interspersed across the acquisition phase (Phase 1). On saline days, sucrose was intermittently available. On nicotine days, sucrose was withheld. All rats acquired the discrimination with increased goal-tracking rates on saline days relative to nicotine days. Following acquisition, rats were separated into four groups to assess drug-substitution and discrimination reversal in Phase 2. The first group maintained the stimulus-reinforcer relation from acquisition (NIC-). The reversal group was now given access to sucrose on nicotine days (NIC+). The substitution group replaced nicotine with varenicline (1 mg/kg) while maintaining the acquisition stimulus-reinforcer relation (VAR-). The substitution and reversal group had nicotine replaced by varenicline and the stimulus-reinforcer relation reversed (VAR+). Rats in all groups learned or maintained their Phase 1 discriminations. For Phase 2, the reversal groups (+ conditions) acquired their discriminations within 10 sessions. The VAR- group displayed a pattern of disrupted discrimination at the outset of Phase 2 but was reestablished after continued training. In substitution testing, VAR groups received nicotine and NIC groups received varenicline. The NIC- and VAR- groups displayed full substitution of the test stimulus whereas the NIC+ and VAR+ groups displayed partial substitution of the test stimulus. Rats underwent nicotine extinction in Phase 3. Initial responding for each group mimicked Phase 2 training (i.e., higher responding by the reversal groups). All rats maintained similarly low levels of responding after six sessions. In conclusion, initial learning history with nicotine (i.e., + or -) influenced drug-stimulus substitution and the rate at which new learning (e.g., reversal) occurs with the varenicline and nicotine interoceptive stimuli.
尼古丁和伐仑克林（Chantix®；领先的非尼古丁戒烟药理学）可以控制如目标追踪等欲望行为。我们在药物辨别目标追踪（DGT）任务中对大鼠（N=48）进行了测试，每个大鼠在获得阶段（第 1 阶段）期间每天接受皮下注射尼古丁（0.4mg/kg）或盐水（0.9%[w/v]）。在盐水日，间歇性提供蔗糖。在尼古丁日，停止提供蔗糖。所有大鼠在盐水日的目标追踪率相对于尼古丁日增加，从而获得了辨别能力。获得后，将大鼠分为四组，以评估第 2 阶段的药物替代和辨别反转。第一组保持获得阶段的刺激-强化关系（NIC-）。反转组现在在尼古丁日获得蔗糖（NIC+）。替代组用伐仑克林（1mg/kg）替代尼古丁，同时保持获得的刺激-强化关系（VAR-）。替代和反转组用伐仑克林替代尼古丁，并反转刺激-强化关系（VAR+）。所有组的大鼠都学习或维持了第 1 阶段的辨别。对于第 2 阶段，反转组（+条件）在 10 次试验中获得了辨别。VAR-组在第 2 阶段开始时显示出辨别紊乱的模式，但在继续训练后得以重建。在替代测试中，VAR 组接受尼古丁，NIC 组接受伐仑克林。NIC-和 VAR-组显示出对测试刺激的完全替代，而 NIC+和 VAR+组显示出对测试刺激的部分替代。大鼠在第 3 阶段接受尼古丁消退。每个组的初始反应都模仿第 2 阶段的训练（即，反转组的反应更高）。所有组在六次试验后都保持类似的低反应水平。总之，与尼古丁的初始学习史（即+或-）影响药物-刺激替代以及伐仑克林和尼古丁内感受性刺激的新学习（例如反转）的发生速度。
