title: Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats.
abstract: The popularity of electronic cigarettes (ECs) has increased dramatically despite their unknown health consequences. Because the abuse liability of ECs is one of the leading concerns of the Food and Drug Administration (FDA), models to assess it are urgently needed to inform FDA regulatory decisions regarding these products. The purpose of this study was to assess the relative abuse liability of an EC liquid compared to nicotine alone in rats. Because this EC liquid contains non-nicotine constituents that may enhance its abuse liability, we hypothesized that it would have greater abuse liability than nicotine alone.
  
  
  
  Nicotine alone and nicotine dose-equivalent concentrations of EC liquid were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, acquisition of self-administration, reinforcing efficacy (i.e., elasticity of demand), blockade of these behavioral effects by mecamylamine, nicotine pharmacokinetics and nicotinic acetylcholine receptor binding and activation.
  
  
  
  There were no significant differences between formulations on any measure, except that EC liquid produced less of an elevation in ICSS thresholds at high nicotine doses.
  
  
  
  Collectively, these findings suggest that the relative abuse liability of this EC liquid is similar to that of nicotine alone in terms of its reinforcing and reinforcement-enhancing effects, but that it may have less aversive/anhedonic effects at high doses. The present methods may be useful for assessing the abuse liability of other ECs to inform potential FDA regulation of those products.
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States; Department of Medicine, University of Minnesota, Minneapolis, MN, United States; Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, United States. Electronic address: lesag002@umn.edu.
authors.forename: M G
authors.initials: MG
authors.lastname: LeSage
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
authors.forename: M
authors.initials: M
authors.lastname: Staley
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
authors.forename: P
authors.initials: P
authors.lastname: Muelken
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States; Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, United States.
authors.forename: J R
authors.initials: JR
authors.lastname: Smethells
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.
authors.forename: I
authors.initials: I
authors.lastname: Stepanov
authors.affiliation: Masonic Cancer Center Biostatistics and Bioinformatics Core, University of Minnesota, Minneapolis, MN, United States.
authors.forename: R I
authors.initials: RI
authors.lastname: Vogel
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States; Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
authors.forename: P R
authors.initials: PR
authors.lastname: Pentel
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, United States; Department of Medicine, University of Minnesota, Minneapolis, MN, United States; Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, United States.
authors.forename: A C
authors.initials: AC
authors.lastname: Harris
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D066300:Electronic Nicotine Delivery Systems; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage; D018733:Nicotinic Antagonists / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D012653:Self Stimulation / Q000187:drug effects*
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine
keywords: Behavioral economics; E-cigarettes; Intracranial self-stimulation; Nicotine; Rat; Self-administration; Tobacco control policy