Schaefer G J, Michael R P
Neuropharmacology. 1986 Feb;25(2):125-31. doi: 10.1016/0028-3908(86)90033-x.
The acute effects of nicotine (0.03-1.0 mg/kg) were studied in a locomotor activity procedure and in a series of intracranial self-stimulation (ICSS) paradigms. Nicotine produced a dose-dependent decrease in locomotor activity. When animals were trained to lever-press for intracranial self-stimulation on a continuous reinforcement schedule (CRF), the drug was ineffective except at the 1.0 mg/kg dose, which produced a moderate decrease in the rate of responding. However, when animals were tested in a fixed-ratio:15 (FR:15) paradigm, nicotine produced a steep, biphasic dose-response curve. At the 0.1 mg/kg dose, the response rates were increased to approx. 60% above baseline, while at the 1.0 mg/kg dose, response rates were decreased to approx. 90% below baseline values. The effects of nicotine were also studied in an auto-titration procedure which measured the rewarding value of the stimulus. There was a decrease in performance at larger doses similar to that observed in the continuous reinforcement procedure, but there were no significant changes in the threshold for reinforcement. Nicotine did not produce any change in the detection threshold for stimulation of the brain. In acute studies, therefore, nicotine produced both stimulation and disruption of behavior, effects that were brought to light by the fixed-ratio schedule of reinforcement, and this may relate to the rewarding effects of nicotine.
在一项自发活动实验以及一系列颅内自我刺激(ICSS)范式中,研究了尼古丁(0.03 - 1.0毫克/千克)的急性效应。尼古丁使自发活动呈剂量依赖性降低。当动物在连续强化程序(CRF)下接受训练以按压杠杆进行颅内自我刺激时,该药物无效,除非剂量为1.0毫克/千克,此剂量会使反应率适度降低。然而,当动物在固定比率15(FR:15)范式下进行测试时,尼古丁产生了一条陡峭的双相剂量反应曲线。在0.1毫克/千克剂量时,反应率增加至比基线水平高出约60%,而在1.0毫克/千克剂量时,反应率降低至比基线值低约90%。还在一种自动滴定程序中研究了尼古丁的效应,该程序测量刺激的奖赏价值。在较大剂量下表现下降,类似于在连续强化程序中观察到的情况,但强化阈值没有显著变化。尼古丁对脑刺激的检测阈值没有产生任何变化。因此,在急性研究中,尼古丁既产生了行为刺激又造成了行为干扰,这些效应通过固定比率强化程序得以显现,这可能与尼古丁的奖赏效应有关。