Research ReportsSignificant association of nicotine reinforcement and cue reactivity: a translational study in humans and ratsButler, Kevina; Forget, Benoîtb; Heishman, Stephen J.c; Le Foll, Bernarda,,d–iAuthor Information aTranslational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada bDepartment of Neuroscience, Pasteur Institute, Paris, France cNational Institute on Drug Abuse, Intramural Research Program, Baltimore, USA dAcute Care Program eCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health fDepartment of Family and Community Medicine gDepartment of Pharmacology and Toxicology hDepartment of Psychiatry, Division of Brain and Therapeutics iInstitute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada Received 28 April 2020 Accepted as revised 6 October 2020 Correspondence to Dr Bernard Le Foll, Centre for Addiction and Mental Health, 33 Ursula Franklin Street, Toronto, Ontario, M5S 2S1, Canada, Tel: +1 416 535 8501; e-mail: [email protected] Behavioural Pharmacology: April 2021 - Volume 32 - Issue 2&3 - p 212-219 doi: 10.1097/FBP.0000000000000607 Buy Metrics Abstract Relapse is common amongst smokers attempting to quit and tobacco cue-induced craving is an important relapse mechanism. Preclinical studies commonly use cue-induced reinstatement of nicotine seeking to investigate relapse neurobiology. Previous research suggests dependence severity and nicotine intake history affect smoking resumption and cue-induced reinstatement of nicotine seeking. However, behavioural data may be interpreted in terms of nicotine reinforcement. This translational study investigated if individual differences in objectively assessed nicotine reinforcement strength were associated with cue-reactivity in both rats and human smokers, which to our knowledge has not been investigated before. Rats (n = 16) were trained to self-administer nicotine and were tested on a progressive ratio schedule of nicotine reinforcement, to assess reinforcer strength, and on a test of cue-induced reinstatement of nicotine seeking. Nicotine reinforcement strength was assessed in human smokers (n = 104) using a forced choice task (nicotine containing vs. denicotinised cigarettes) and self-reported cue-induced craving was assessed following exposure to smoking and neutral cues. Responding for nicotine under progressive ratio was strongly positively correlated with cue-induced reinstatement of nicotine seeking in rats. Nicotine choices in human smokers were significantly associated with cue-induced craving controlling for dependence severity, years of smoking, and urge to smoke following neutral cues. Findings suggest nicotine reinforcement strength is associated with both types of cue-induced behaviour, implying some translational commonality between cue-induced craving in human smokers and cue-induced reinstatement of nicotine seeking in rats. Findings are discussed in relation to clinical implications and whether these laboratory tasks assess drug ‘wanting’. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.