Karatayev Olga, Lukatskaya Olga, Moon Sang-Ho, Guo Wei-Ran, Chen Dan, Algava Diane, Abedi Susan, Leibowitz Sarah F
Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Alcohol. 2015 Aug;49(5):479-89. doi: 10.1016/j.alcohol.2015.03.002. Epub 2015 Apr 11.
Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol.
临床研究表明，尼古丁滥用和酒精滥用常常并存，这可能部分归因于人们容易获取并摄入富含脂肪的饮食。动物研究显示，成年动物摄入高脂饮食会增加尼古丁或乙醇的消耗量，孕期母鼠摄入富含脂肪的饮食会增加子代对尼古丁的操作性反应，但关于膳食脂肪对这两种药物共同滥用的影响，人们所知甚少。本研究的目的是在长 Evans 大鼠中，采用一种涉及同时静脉注射（IV）自我给药这两种药物的新范式，测试围产期暴露于脂肪对尼古丁和乙醇共同使用的影响。对暴露于脂肪与普通饲料的子代进行特征描述和比较，首先比较它们的尼古丁自我给药行为，然后比较它们的尼古丁/乙醇自我给药行为，最后比较它们在无尼古丁情况下的乙醇自我给药行为。结果表明，与孕期和哺乳期摄入低脂普通饲料相比，母鼠摄入脂肪会在固定比率测试中显著刺激尼古丁自我给药。在固定比率和剂量反应测试中，它还会增加尼古丁/乙醇自我给药，使血液乙醇浓度（BEC）升高至 120mg/dL，并在渐进比率测试中导致断点增加。特别值得注意的是，与仅给予尼古丁相比，围产期暴露于脂肪的大鼠自我给药的尼古丁/乙醇混合物显著更多，这种效应在普通饲料对照大鼠中并不明显。从尼古丁/乙醇混合物中去除尼古丁后，脂肪暴露组和普通饲料暴露组大鼠之间的这种差异消失，两组均未能学会单独自我给药乙醇。总之，这些发现表明，围产期暴露于富含脂肪的饮食，除了刺激尼古丁自我给药外，还会使机体更易过度同时使用尼古丁和乙醇。
