+ Models PNEC-1681; No of Pages 8 Please cite this article in press as: von der Goltz, C., et al., Orexin and leptin are associated with nicotine craving: A link between smoking, appetite and reward. Psychoneuroendocrinology (2009), doi:10.1016/j.psyneuen.2009.09.005 Orexin and leptin are associated with nicotine craving: A link between smoking, appetite and reward Christoph von der Goltz a, * , Anne Koopmann a , Christina Dinter a , Anne Richter a , Christine Rockenbach a , Martin Grosshans a , Helmut Nakovics a , Klaus Wiedemann b , Karl Mann a , Georg Winterer c , Falk Kiefer a a Dept. of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health (CIMH), Square J5, 68159 Mannheim, Germany b Dept. of Psychiatry, University Hospital of Hamburg, Martinistr. 52, 20246 Hamburg, Germany c Dept. of Psychiatry, Heinrich-Heine University, Bergische Landstr. 2, 40629 Du ¨sseldorf, Germany Received 6 May 2009; received in revised form 2 September 2009; accepted 4 September 2009 1. Introduction Smoking is a major risk factor for a number of preventable diseases including lung cancer, cardiovascular and chronic obstructive pulmonary diseases. It is estimated that in the Psychoneuroendocrinology (2009) xxx, xxx—xxx * Corresponding author. Tel.: +49 62117033722; fax: +49 62117033505. E-mail address: christoph.goltz@zi-mannheim.de (C. von der Goltz). KEYWORDS Nicotine; Orexin; Hypocretin; Leptin; Craving; QSU; Tobacco; Smoking Summary Objective: Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions. Methods: We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n = 60) during early nicotine withdrawal and healthy controls (n = 64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU). Results: As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r = 0.28; p < .05), and a positive association between craving and leptin plasma concentration (r = 0.29; p < .05). Conclusions: Our results show an association between craving for nicotine and plasma concen- trations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine. # 2009 Elsevier Ltd. All rights reserved. available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/psyneuen 0306-4530/$ — see front matter # 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2009.09.005