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The Effects of Stress on Levels of Nicotine in the Rat

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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The present study was designed to determine if a stress reduces nicotine levels in the body b if reduced levels could be explained by increased rates of nicotinemetabolism. Levels of nicotine in the tissues blood, fat, muscle, and brain of stressed and nonstressed Sprague-Dawley rats were compared in order to determine if stress would lower nicotine levels in the rat. In addition, nicotine metabolism was measured both in vivo and in vitro in order to determine if stress might exert its effects on nicotine levels directly by increasing the rate of conversion of nicotine to cotinine, nicotines primary metabolite. Blood levels of cotinine were measured to determine nicotine metabolism in vivo. Livers were harvested and incubated with nicotine and the incubates were analyzed for cotinine to determine nicotine metabolism in vitro. Animals were administered one of three dosages of nicotine 0, 6, and 12 mg nicotinekg via miniosmotic pumps implanted subcutaneously. After 14 days of continuous drug administration, animals were subjected to one of three conditions no stress, noise stress, and rubber ligature stress for 2.5 hours. Immediately following this 2.5 h period, animals were sacrificed and tissue nicotine and blood and liver cotinine levels were determined. Comparing animals receiving 12 mg nicotinekgday, blood nicotine levels were lower among animals in the noise and rubber ligature conditions compared to animals in the nonstress condition. There was no effect of stress condition on either measure of nicotine metabolism. These results are consistent with the explanation that smokers under stress smoke more to replace lost nicotine. In addition, the fact that reductions in nicotine levels were observed comparing animals in the 12 mg nicotinekgday, but not among animals in the 6 mgkgday conditions, suggests that drug dosage is an important factor in this relationship.

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