Short ReportEarly adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague–Dawley ratsCardenas, Anjelicaa; Martinez, Maricelab; Saenz Mejia, Alejandrac; Lotfipour, Shahrdada,,dAuthor Information aDepartment of Pharmaceutical Sciences bDepartment of Psychological Sciences cDepartment of Biological Sciences dDepartment of Emergency Medicine, University of California Irvine, Irvine, California, USA Received 21 April 2020 Accepted as revised 19 August 2020 Correspondence to Shahrdad Lotfipour, PhD, Department of Emergency Medicine, University of California Irvine, 303 Med Surge II, Irvine, CA 92612, USA, E-mail: [email protected] Behavioural Pharmacology: February 2021 - Volume 32 - Issue 1 - p 86-91 doi: 10.1097/FBP.0000000000000593 Buy Metrics Abstract An exponential rise in nicotine-containing electronic-cigarette use has been observed during the period of adolescence. Preclinical studies have shown that nicotine exposure during early adolescence, but not adulthood, increases subsequent drug intake and reward. Although growing clinical trends highlight that stimulant use disorders are associated with the opioid epidemic, very few studies have assessed the effects of adolescent nicotine exposure on opioid intake. The objective of our current study is to develop a new animal model to assess the causal relationship of adolescent nicotine exposure on subsequent opioid intake. In this effort, we first replicate previous studies using a well-established 4-day nicotine paradigm. Rats are pretreated with a low dose of nicotine (2 × , 30 μg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days 28–31) or adulthood (postnatal days 86–89). Following nicotine pretreatment on postnatal day 32 or postnatal day 90, animals underwent operant intravenous self-administration for the psychostimulant, cocaine [500 μg/kg/infusion (inf)] or the opioid, fentanyl (2.5 μg/kg/inf). We successfully show that adolescent but not adult, nicotine exposure enhances cocaine self-administration in male rats. Furthermore, we illustrate early adolescent but not adult nicotine exposure enhances fentanyl self-administration, independent of sex. Overall, our findings highlight that adolescence is a unique period of development that is vulnerable to nicotine-induced enhancement for cocaine and fentanyl self-administration in rats. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.