Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.
Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.
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DOI：
10.1111/adb.12263
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Markou A
中科院分区：
文献类型：
--
作者：
Boutros N;Semenova S;Markou A
许多青少年酗酒。有限的人体研究表明，青少年饮酒预示着成人吸烟。本研究调查了青春期间歇性乙醇(AIE)暴露是否会改变成年后的尼古丁敏感性。成年雄性Wistar大鼠(出生后28-53天)暴露于AIE，剂量为5g/kg的25%乙醇，每天3次，共2天，共2天。对照组大鼠接受相同暴露方案的水。成年后，对不同组的大鼠进行尼古丁静脉自我注射(IVSA)、药物辨别和条件性味觉厌恶(CTA)测试。在固定比例强化方案下，AIE暴露大鼠和对照组大鼠尼古丁IVSA的剂量-反应函数相似。然而，暴露于AIE的大鼠在最低剂量下自身摄入的尼古丁较少，这表明与对照组相比，低剂量尼古丁对暴露于AIE的大鼠的增强作用较小。暴露于AIE的大鼠在递增比例的时间表下自我给予较少的尼古丁，这表明AIE暴露后对尼古丁的动机降低。与对照组相比，暴露于AIE的大鼠对尼古丁的辨别刺激作用减弱。没有观察到尼古丁CTA的组间差异，这表明AIE暴露对尼古丁的厌恶特性没有影响。总之，这些结果表明，AIE暴露降低了成年大鼠对尼古丁的增强、激励和区分特性的敏感性，而保持尼古丁的厌恶特性不变。这些发现表明，青春期饮酒可能会导致成年人对尼古丁的敏感度降低，这可能反过来导致吸烟率更高。
Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28–53) were exposed to AIE exposure that consisted of 5 g/kg of 25% ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination, and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational, and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking.