尼古丁自我给药的奖赏效应在雄性和雌性大鼠中随时间推移而增加。
Rewarding Effects of Nicotine Self-administration Increase Over Time in Male and Female Rats.
机构信息
Department of Psychiatry, University of Florida, Gainesville, FL, USA.
Department of Neuroscience, University of Florida, Gainesville, FL, USA.
出版信息
Nicotine Tob Res. 2021 Nov 5;23(12):2117-2126. doi: 10.1093/ntr/ntab097.
INTRODUCTION
Smoking and the use of other nicotine-containing products is rewarding in humans. The self-administration of nicotine is also rewarding in male rats. However, it is unknown if there are sex differences in the reward-enhancing effects of nicotine self-administration and if the rewarding effects of nicotine change over time.
METHODS
Rats were prepared with catheters and intracranial self-stimulation (ICSS) electrodes to investigate the effects of nicotine and saline self-administration on reward function. A decrease in thresholds in the ICSS procedure reflects an enhancement of reward function. The ICSS parameters were determined before and after the self-administration sessions from days 1 to 10, and after the self-administration sessions from days 11 to 15.
RESULTS
During the first 10 days, there was no sex difference in nicotine intake, but during the last 5 days, the females took more nicotine than the males. During the first 10 days, nicotine self-administration did not lower the brain reward thresholds but decreased the response latencies. During the last 5 days, nicotine lowered the reward thresholds and decreased the response latencies. An analysis with the 5-day averages (days 1-5, 6-10, and 11-15) showed that the reward enhancing and stimulatory effects of nicotine increased over time. There were no sex differences in the reward-enhancing and stimulatory effects of nicotine. The nicotinic receptor antagonist mecamylamine diminished the reward-enhancing and stimulatory effects of nicotine.
CONCLUSION
These findings indicate that the rewarding effects of nicotine self-administration increase over time, and there are no sex differences in the reward-enhancing effects of nicotine self-administration in rats.
IMPLICATIONS
This study investigated the rewarding effect of nicotine and saline self-administration in male and female rats. The self-administration of nicotine, but not saline, enhanced brain reward function and had stimulatory effects. The rewarding effects of nicotine increased over time in the males and the females. Despite that the females had a higher level of nicotine intake than the males, the reward-enhancing effects of nicotine self-administration were the same. These findings suggest that in new tobacco and e-cigarette users, nicotine's rewarding effects might increase quickly, and a higher level of nicotine use in females might not translate into greater rewarding effects.
简介
吸烟和使用其他含尼古丁的产品会给人类带来愉悦感。尼古丁的自我给药在雄性大鼠中也是令人愉悦的。然而，目前尚不清楚尼古丁自我给药的奖赏增强效应是否存在性别差异，以及尼古丁的奖赏效应是否随时间而变化。
方法
通过使用导管和颅内自我刺激（ICSS）电极，对雄性和雌性大鼠进行尼古丁和盐水自我给药对奖赏功能的影响的研究。ICSS 程序中的阈值降低反映了奖赏功能的增强。在第 1 至 10 天的自我给药期前后，以及第 11 至 15 天的自我给药期前后，确定了 ICSS 参数。
结果
在前 10 天，雄性和雌性大鼠的尼古丁摄入量没有性别差异，但在后 5 天，雌性大鼠的尼古丁摄入量高于雄性大鼠。在前 10 天，尼古丁自我给药不会降低大脑奖赏阈值，但会缩短反应潜伏期。在后 5 天，尼古丁降低了奖赏阈值并缩短了反应潜伏期。对 5 天平均值（第 1-5 天、第 6-10 天和第 11-15 天）的分析表明，尼古丁的奖赏增强和刺激作用随时间增加。尼古丁的奖赏增强和刺激作用在雄性和雌性大鼠中没有性别差异。烟碱型乙酰胆碱受体拮抗剂美加明减弱了尼古丁的奖赏增强和刺激作用。
结论
这些发现表明，尼古丁自我给药的奖赏作用随时间增加，且雄性和雌性大鼠尼古丁自我给药的奖赏增强作用无性别差异。
意义
本研究调查了雄性和雌性大鼠尼古丁和盐水自我给药的奖赏效应。尼古丁的自我给药增强了大脑的奖赏功能并具有刺激作用，而盐水的自我给药没有这种作用。在雄性和雌性大鼠中，尼古丁的奖赏作用随时间的增加而增加。尽管雌性大鼠的尼古丁摄入量高于雄性大鼠，但尼古丁自我给药的奖赏增强作用是相同的。这些发现表明，在新的烟草和电子烟使用者中，尼古丁的奖赏作用可能会迅速增加，而女性较高的尼古丁使用量可能不会转化为更大的奖赏作用。
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