Nicotine Administration Robustly Enhances Fentanyl-Induced Dopamine Transmission within the Dorsolateral Striatum
Abstract
Opioid use disorder is a prevalent public health concern in the United States. Approximately 70% of all drug overdose deaths are attributable to fentanyl, demonstrating a need to identify risk factors underlying the escalation of fentanyl use. Nicotine use is a risk factor associated with increased consumption of opioids across both clinical and preclinical populations. Our prior findings show that nicotine administration escalates consumption of opioids and that this elevated consumption persists despite adverse consequences in rodents, demonstrating a behavioral phenotype resembling those that emerge following protracted experience with opioids. Prolonged drug consumption is associated with a shift toward increased dopamine (DA) transmission within dorsolateral striatum (DLS), a brain area critical for the development of inflexible behaviors. The present study sought to characterize the behavioral and neurochemical effects of nicotine on fentanyl administration. A dose–response curve was used to determine the effect of nicotine on fentanyl consumption as a function of dose in males and females. Systemic pretreatment with nicotine-enhanced fentanyl intake across all doses relative to nicotine-naive controls, suggesting that nicotine augments responding for opioids without evident effects on sensitivity to fentanyl. Additionally, fast-scan cyclic voltammetry was applied to measure DLS DA transmission in response to fentanyl administration and to quantify any effect of nicotine on this response in male rats. Fentanyl administration enhanced DA concentrations within DLS, and this effect was potentiated by nicotine pretreatment. These findings support that enhanced DA transmission in DLS may mechanistically contribute to nicotine-induced increases in the motivation for opioids.
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BibTeX
@article{bhimani2026nicotine,
title = {{Nicotine Administration Robustly Enhances Fentanyl-Induced Dopamine Transmission within the Dorsolateral Striatum}},
author = {Rohan V. Bhimani and Sarah C. Honeycutt and Gregory Carl Loney and Jinwoo Park},
journal = {eneuro},
year = {2026},
month = oct,
doi = {10.1523/eneuro.0161-26.2026},
url = {https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0161-26.2026},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - Nicotine Administration Robustly Enhances Fentanyl-Induced Dopamine Transmission within the Dorsolateral Striatum
AU - Rohan V. Bhimani
AU - Sarah C. Honeycutt
AU - Gregory Carl Loney
AU - Jinwoo Park
PY - 2026
DA - 2026/10/09
JO - eneuro
DO - 10.1523/eneuro.0161-26.2026
UR - https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0161-26.2026
AB - Opioid use disorder is a prevalent public health concern in the United States. Approximately 70% of all drug overdose deaths are attributable to fentanyl, demonstrating a need to identify risk factors underlying the escalation of fentanyl use. Nicotine use is a risk factor associated with increased consumption of opioids across both clinical and preclinical populations. Our prior findings show that nicotine administration escalates consumption of opioids and that this elevated consumption persists despite adverse consequences in rodents, demonstrating a behavioral phenotype resembling those that emerge following protracted experience with opioids. Prolonged drug consumption is associated with a shift toward increased dopamine (DA) transmission within dorsolateral striatum (DLS), a brain area critical for the development of inflexible behaviors. The present study sought to characterize the behavioral and neurochemical effects of nicotine on fentanyl administration. A dose–response curve was used to determine the effect of nicotine on fentanyl consumption as a function of dose in males and females. Systemic pretreatment with nicotine-enhanced fentanyl intake across all doses relative to nicotine-naive controls, suggesting that nicotine augments responding for opioids without evident effects on sensitivity to fentanyl. Additionally, fast-scan cyclic voltammetry was applied to measure DLS DA transmission in response to fentanyl administration and to quantify any effect of nicotine on this response in male rats. Fentanyl administration enhanced DA concentrations within DLS, and this effect was potentiated by nicotine pretreatment. These findings support that enhanced DA transmission in DLS may mechanistically contribute to nicotine-induced increases in the motivation for opioids.
SN - 2373-2822
ER -