Tobacco smoking is used to control food intake and body weight gain. Conversely, tobacco smoking cessation has been associated with increased food intake and accelerated body weight gain. Evidence indicates that smoking helps to control food intake by elevating adiposity signals (e.g., insulin and leptin) that modulate neurobehavioral processes. We hypothesize that chronic administration of nicotine results in adaptations in adiposty signaling in brain areas involved in food motivation. Upon cessation of nicotine administration these adaptations remain unopposed which leads to increased food intake. The first specific aim examines the effects of chronic nicotine administration on insulin and leptin signaling in two brain areas involved in food motivation, the arcuate hypothalamic nucleus and the ventral tegmental area. The intracranial self-stimulation procedure (ICSS) will be used to assess the effects of nicotine on adiposity signaling as it provides a quantitative measure of the motivational effects of changes in central adiposity signaling. Administration of insulin and leptin elevates brain reward thresholds, which is indicative of a decreased sensitivity to the electrical stimuli. It is expected that the threshold elevating effects of insulin and leptin are reduced during and after chronic exposure to nicotine. In addition, it is expected that plasma insulin and leptin levels are elevated during nicotine administration and return to baseline levels after cessation of nicotine administration. This pattern of results would suggest that that a decreased central responsivity to insulin or leptin mediates the increased food motivation associated with smoking cessation. Overweight adolescents are more likely to initiate tobacco smoking and develop a nicotine dependency than non-overweight adolescents. We hypothesize that the hormonal changes and neuroadaptations associated with diet-induced obesity potentiate the rewarding effects of nicotine and thereby accelerate the transition from experimenting with cigarettes to habitual smoking.
Specific aim 2 examines the effects of diet-induced obesity on the rewarding effects of nicotine using the rat ICSS paradigm. Taken together, these proposed studies will start exploring the interplay between adiposity signaling and the rewarding effects of nicotine. Quitting smoking increases food intake and body weight gain. The studies described in this grant application investigate why quitting smoking leads to increased food intake and body weight gain. A better understanding of the brain mechanisms underlying post-cessation weight gain may contribute to new treatments for post-cessation weight gain and thereby improve smoking cessation rates.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Small Research Grants (R03)
Project #
Application #
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rapaka, Rao
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Florida
Schools of Medicine
United States
Zip Code
Bruijnzeel, Adrie W; Qi, Xiaoli; Corrie, Lu W (2013) Anorexic effects of intra-VTA leptin are similar in low-fat and high-fat-fed rats but attenuated in a subgroup of high-fat-fed obese rats. Pharmacol Biochem Behav 103:573-81
Bruijnzeel, Adrie W; Corrie, Lu W; Rogers, Jessica A et al. (2011) Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats. Behav Brain Res 219:254-64
Bruijnzeel, Adrie W (2009) kappa-Opioid receptor signaling and brain reward function. Brain Res Rev 62:127-46
Rylkova, Daria; Boissoneault, Jeffrey; Isaac, Shani et al. (2008) Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. Neuropeptides 42:215-27
Bruijnzeel, Adrie W; Zislis, George; Wilson, Carrie et al. (2007) Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 32:955-63
Bruijnzeel, Adrie W; Marcinkiewcz, Catherine; Isaac, Shani et al. (2007) The effects of buprenorphine on fentanyl withdrawal in rats. Psychopharmacology (Berl) 191:931-41