Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler, Montreal, Québec, H3G 1Y6, Canada.
Psychopharmacology (Berl). 2018 Mar;235(3):803-814. doi: 10.1007/s00213-017-4796-1. Epub 2017 Dec 3.
Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction.
Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction.
Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine.
Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.
尼古丁和 D-苯丙胺可以增强非条件视觉刺激的强化效应。我们研究了这些增强强化效应是否反映了刺激习惯化的减缓，以及是否依赖于食物限制。
成年雄性大鼠在每天 60 分钟的时段内按压主动杆使提示灯发光。根据实验的不同，大鼠接受固定或变化剂量的 D-苯丙胺（0.25-2mg/kg IP）和尼古丁（0.025-0.2mg/kg SC）或烟草成分去甲哈尔曼（0.03-10μg/kg IV）的挑战。实验 1 测试了 D-苯丙胺和去甲哈尔曼可能具有的增强强化作用。实验 2 研究了尼古丁和苯丙胺是否抑制了主动杆按压在会话内的自发下降。实验 3 评估了食物限制的影响。
苯丙胺（0.25-1mg/kg）和尼古丁（0.1mg/kg）特异性地增加了主动杆按压（增加两到三倍）。尼古丁和苯丙胺的最高剂量也影响了非主动杆反应（分别增加和减少）。在省略视觉强化物的情况下，反应主要被消除。两种药物似乎都没有减缓习惯化，这可以通过会话内主动杆按压的下降来评估，并且如果在这种下降发生后给予药物，增强强化效应仍然会发生。食物限制增强了苯丙胺的增强强化效应，但不是尼古丁的。
在经过数周的测试后，反应仍然是有目的的。即使在自由喂养的动物中，低剂量的 D-苯丙胺和尼古丁也会产生强化增强作用，而与反应在会话内的自发下降无关。苯丙胺的强化增强作用，但不是尼古丁的，通过同时进行的亚慢性食物限制得到增强。
