Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuropharmacology. 2018 Jan;128:33-42. doi: 10.1016/j.neuropharm.2017.09.029. Epub 2017 Sep 21.

Evaluating oral flavorant effects on nicotine self-administration behavior and phasic dopamine signaling.

Author information

1
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, United States.
2
Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, United States.
3
Department of Biotechnical and Clinical Laboratory Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, United States.
4
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, United States; Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, United States; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06511, United States. Electronic address: nii.addy@yale.edu.

Abstract

Understanding how tobacco product flavor additives, such as flavorants in electronic cigarettes, influence smoking behavior and addiction is critical for informing public health policy decisions regarding tobacco product regulation. Here, we developed a combined intraoral (i.o.) and intravenous (i.v.) self-administration paradigm in rats to determine how flavorants influence self-administration behavior. By combining i.o. flavorant delivery with fast scan cyclic voltammetry (FSCV) or i.v. nicotine self-administration in adult, male rats, we examined whether flavors alter phasic dopamine (DA) signaling and nicotine self-administration. Oral administration of 10% sucrose or 0.32% saccharin, but not 0.005% menthol, increased phasic DA release in the nucleus accumbens (NAc). Oral sucrose or saccharin, when combined with i.v. nicotine delivery, also led to increased self-administration behavior. Specifically, combined i.o. sucrose and i.v. nicotine decreased responding compared to sucrose alone, and increased responding compared to nicotine alone. In contrast, i.o. flavorants did not alter motivational breakpoint in a progressive ratio task. Oral menthol, which did not alter i.v. nicotine administration, reversed oral nicotine aversion (50 and 100 mg/L) in a two-bottle choice test. Here, we demonstrate that i.o. appetitive flavorants that increase phasic DA signaling also increase self-administration behavior when combined with i.v. nicotine delivery. Additionally, oral menthol effects were specific to oral nicotine, and were not observed with i.v. nicotine-mediated reinforcement. Together, these preclinical findings have important implications regarding menthol and sweet flavorant additive effects on tobacco product use and can be used to inform policy decisions on tobacco product flavorant regulation.

KEYWORDS:

Menthol; Nucleus accumbens; Progressive ratio; Saccharin; Sucrose; Voltammetry

PMID:
28943284
PMCID:
PMC5714675
[Available on 2019-01-01]
DOI:
10.1016/j.neuropharm.2017.09.029
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center