Chronic tobacco smoking, a worldwide leading cause of mortality, results from a highly addictive state associated with the consumption of nicotine, the major psychoactive ingredient in tobacco products. Despite several reports in human smokers, it is still unknown to what degree psychological states such as stress and anxiety enhance the motivation to consume nicotine. With the aid of a novel model of nicotine-seeking behavior in rats, the proposed research is intended to elucidate the impact on nicotine-seeking behavior of stressful or anxiogenic stimuli. In preliminary work, we have demonstrated that rats will traverse a long straight-arm runway and enter a goal box for a single daily intravenous injection of nicotine (0.01 - 0.09 mf/kg/inj). Since animals are tested but once a day, the speed with which they run the alley provides a reliable assay for the non-drugged subjects'motivation to seek nicotine - and indeed we have shown dose- dependent changes in running speed with a maximal performance for a dose of 0.03 mg/kg/inj. The current application builds upon these results and proposes experiments intended to accomplish a single specific aim: to examine the impact of stress-inducing or anxiogenic stimuli on nicotine-seeking behavior. This research will assess whether or not the presence of pharmacologically-induced """"""""anxiety"""""""" or restraint- induced stress produce shifts in the dose-response curve for nicotine reinforcement. These data will therefore serve to assess the viability of our runway model (which has been used successfully for the study of other drugs of abuse) to the study of nicotine-seeking behavior, and carefully establish the impact of stressful and/or anxiogenic stimuli on the motivation to seek nicotine in laboratory rats.
|Owen, David M; Huang, Hua; Ye, Jin et al. (2009) Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor. Virology 394:99-108|