Age-Related Differences in the Disposition of Nicotine and Metabolites in Rat Brain and Plasma

被引:19
|
作者
Vieira-Brock, Paula L. [1 ]
Andrenyak, David M. [2 ]
Nielsen, Shannon M. [1 ]
Fleckenstein, Annette E. [1 ]
Wilkins, Diana G. [1 ,2 ]
机构
[1] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA
[2] Univ Utah, Ctr Human Toxicol, Salt Lake City, UT 84112 USA
基金
美国国家卫生研究院;
关键词
CONDITIONED PLACE PREFERENCE; ADULT RATS; ADOLESCENT; CYP2A6; VULNERABILITY; NORNICOTINE; DEPENDENCE; PERIADOLESCENT; EXPRESSION; WITHDRAWAL;
D O I
10.1093/ntr/ntt067
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Introduction: Studies have evaluated the behavioral and neurochemical impact of nicotine administration in rodents. However, the distribution of nicotine and metabolites in rat brain and plasma as a function of age has not been investigated. This is a significant issue because human adolescents have a greater risk for developing nicotine addiction than adults, and reasons underlying this observation have not been fully determined. Thus, in this present study, we evaluated the impact of the transition from adolescence (postnatal day [PND 40]) to adulthood (PND 90) on nicotine distribution in rats. Methods: PND 40, 60, and 90 rats received a single injection of (-) nicotine (0.8 mg/kg, subcutaneously). Liquid chromatography tandem-mass spectrometry was used to measure concentration of nicotine and metabolites in selected biological matrices. Results: Nicotine, cotinine, and nornicotine were detected in rat striata and frontal cortex 30 min, 1 hr, 2 hr, and 4 hr after a single administration. These and several additional metabolites (nicotine-1'-oxide, cotinine-N-oxide, norcotinine, and trans-3'-hydroxycotinine) were also detected in plasma at these same timepoints. The mean concentration of nicotine in brain and plasma was lower in PND 40 versus PND 90 rats. In contrast, the mean concentration of nornicotine was higher in the plasma and brain of PND 40 versus PND 90 rats. Conclusions: Nicotine and metabolite distribution differs between adolescent and adult rats. These data suggest that adolescent rats metabolize nicotine to some metabolites faster than adult rats. Further studies are needed to investigate the potential correlation between age, drug distribution, and nicotine addiction.
引用
收藏
页码:1839 / 1848
页数:10
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