Research report Hostility differentiates the brain metabolic effects of nicotine James H. Fallon a , David B. Keator b , James Mbogori c , Jessica Turner d , Steven G. Potkin e, * a Department of Anatomy and Neurobiology, University of California, Irvine, BIRN-RP, 5251 California, Suite 240, Irvine, CA 92697-3960, USA b Department of Psychiatry andHuman Behavior, Brain Imaging Center, University of California, Irvine, Irvine Hall, Room 180, Irvine, CA 92697-3960, USA c Department of Psychiatry and Human Behavior, Brain Imaging Center, University of California, Irvine, Irvine Hall, Room 183, Irvine, CA 92697-3960, USA d Department of Psychiatry and Human Behavior, University of California, Irvine, BIRN-RP 5251, California, Suite 240, Irvine, CA 92967-3960, USA e Department of Psychiatry and Human Behavior, Brain Imaging Center, University of California, Irvine, Irvine Hall, Room 163, Irvine, CA 92697-3960, USA Accepted 1 October 2003 Abstract The brain mechanisms underlying the cause of nicotine dependence are unknown, however, hostility traits are associated with increased susceptibility to nicotine dependence. We used FDG PET to measure brain metabolic response to nicotine administered by patch while the subject performed the Bushman aggression task in 86 high- and low-hostility subjects. Low-hostility trait subjects demonstrated no significant change in brain metabolic response to nicotine. In marked contrast, high-hostility non-smokers subjects demonstrated dramatic metabolic changes to low dose (3.5 mg patch) as did high-hostility smokers to high dose nicotine (21 mg patch) throughout the brain bilaterally ( p < 0.025). Correlational analyses demonstrated greater metabolic changes in response to nicotine in subjects with greatest hostility trait measures. The observed differences were not a consequence of plasma nicotine or cotinine levels. These metabolic changes were not observed when subjects performed a sustained attentional task (continuous performance task; CPT). Behaviorally, high-hostility subjects had higher ratings of anger, impatience, irritability and nervousness, and lower ratings of happiness, relaxation and curiosity than low-hostility subjects. Smokers had significantly greater scores on impatience and restlessness than non-smokers. This PET study demonstrates a conspicuous lack of the brain metabolic response to nicotine in low-hostility non-smokers in contrast to a dramatic brain response to nicotine in high hostility subjects. This biological difference in brain metabolic response to nicotine between high and low hostility trait subjects may explain differences in susceptibility to nicotine dependence. D 2003 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Topic: Motivation and emotion Keywords: Nicotine; Smoking; Brain imaging; Hostility; Addiction; PET; Attention; Personality 1. Introduction While the association of hostility and depression person- ality traits with susceptibility to nicotine dependence has been established [1,8,15,16,20], the underlying brain mech- anisms subserving these behaviors are unknown. Hostile acts and hostile thoughts are predictive of smoking behavior [24]. Differences in personality traits have been related to a differential behavioral and attentional response to smoking [17]. The purpose of this study was to investigate the effects of nicotine on regional brain metabolic rate in low-hostility and high-hostility subjects. The personality trait of hostility has been strongly associated with susceptibility to nicotine dependence. We were interested in the brain metabolic effects of nicotine related to hostility personality trait. 2. Materials and methods The brain metabolic activity during the performance of a hostility task was imaged with PET scans. In order to remove the cueing or non-nicotine related effects of smoking, we administered nicotine by patch and compared it to placebo patch in a double-blind, random assignment design. Nicotine was administered in two doses (3.5 and/or 21 mg; Smith Kline Beecham Nicoderm CQ), 3.5 h before injection of 5 0926-6410/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.cogbrainres.2003.10.003 * Corresponding author. Tel.: +1-949-824-8040; fax: +1-949-824- 7873. E-mail address: sgpotkin@uci.edu (S.G. Potkin). www.elsevier.com/locate/cogbrainres Cognitive Brain Research 18 (2004) 142 – 148