OSCR

Utility of the Recombinase Driver CX3CR1-ERT2 Rat Strain in Nicotine Self-Administration.

Overview

Authors: Ashley M White1, Ashley J Craig1, Daryl L Richie1, Christa L Corley1, Percell T Kendrick Jr1, Kathleen R McNealy1, Michael D Scofield2, Cassandra D Gipson1
  1. Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA; (A.M.W.); (A.J.C.); (D.L.R.); (C.L.C.); (P.T.K.J.); (K.R.M.)
  2. Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
Institutions: University of Kentucky (United States); Medical University of South Carolina (United States)
Journal: Cells, volume 15, issue 16, article 1445
Dates: received 7 July 2026; accepted 9 August 2026; published online 11 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3390/cells15161445 · PMID 42645173 · PMCID PMC13511460 · OpenAlex W7202210687
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: rat (organism), cellular / molecular (subfield)
Methods: Statistics
Keywords: microglia, nicotine, self-administration, behavior, DREADDs
MeSH: CX3C Chemokine Receptor 1*, Integrases*, Nicotine*, Animals, Male, Microglia, Nucleus Accumbens, Rats, Rats, Long-Evans, Rats, Transgenic, Self Administration (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: NIDA NIH HHS (R21 DA044479, R33 DA049130, DA061626, R01 DA046526, DA046526, R01 DA058933, R03 DA061626, R21 DA049130, R21 DA055879); NCATS NIH HHS (TL1 TR001997)
Citations: not cited yet (Europe PMC); 51 references in the paper
Research resources: Mouse Anti-NeuN antibody RRID:AB_10711040, DAPI antibody RRID:AB_2629482, AlexaFluor 488 goat anti-chicken IgY RRID:AB_2636995, Anti CX3CR1, Mouse RRID:AB_2916288, Anti Iba1, Rabbit RRID:AB_839504

Abstract

Smoking remains a leading preventable cause of death, and nicotine is the primary substance responsible for maintaining use of tobacco products. Preclinical rodent models have shown that neuroimmune signaling is dysregulated by nicotine self-administration (SA) within the nucleus accumbens core (NAcore). Microglia are the resident brain immune cell and prior studies have shown that they play an important role in nicotine-related behaviors. However, while transgenic mouse lines allow for specific evaluations of microglia to determine their role in neurobiology and behavior, there are fewer tools available for rats as a model species, thus limiting our ability to evaluate specific contributions of microglia to nicotine SA. A transgenic rat expressing Cre under the control of the CX3CR1 promoter bred on a Long–Evans (LE) background was recently developed, and here we show that NAcore microglia can be virally transduced with designer receptors exclusively activated by designer drugs (DREADDs) without neuronal expression. We further show that CX3CR1::ERT2 rats readily self-administer nicotine and display a characteristic extinction curve. Together, these validation studies lay the foundation for future use of this transgenic rat line to evaluate the specific contributions of microglia within the brain reward pathway to the neurobehavioral underpinnings of nicotine addiction.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability Statement

The original data presented in the study are openly available in Harvard Dataverse at https://doi.org/10.7910/DVN/NMEBTZ.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 11 MeSH terms, 2 funders, 50 references, 5 RRIDs.

Cite

This paper

White, A. M., Craig, A. J., Richie, D. L., Corley, C. L., Kendrick, P. T., McNealy, K. R., Scofield, M. D., & Gipson, C. D. (2026). Utility of the Recombinase Driver CX3CR1-ERT2 Rat Strain in Nicotine Self-Administration. Cells, 15(16), 1445. https://doi.org/10.3390/cells15161445

BibTeX

@article{white2026utility,
author = {White, Ashley M and Craig, Ashley J and Richie, Daryl L and Corley, Christa L and Kendrick, Percell T and McNealy, Kathleen R and Scofield, Michael D and Gipson, Cassandra D},
title = {{Utility of the Recombinase Driver CX3CR1-ERT2 Rat Strain in Nicotine Self-Administration}},
journal = {Cells},
year = {2026},
month = aug,
volume = {15},
number = {16},
pages = {1445},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
issn = {2073-4409},
doi = {10.3390/cells15161445},
url = {https://doi.org/10.3390/cells15161445},
pmid = {42645173},
pmcid = {PMC13511460}
}

RIS

TY - JOUR
AU - White, Ashley M
AU - Craig, Ashley J
AU - Richie, Daryl L
AU - Corley, Christa L
AU - Kendrick, Percell T
AU - McNealy, Kathleen R
AU - Scofield, Michael D
AU - Gipson, Cassandra D
TI - Utility of the Recombinase Driver CX3CR1-ERT2 Rat Strain in Nicotine Self-Administration
T2 - Cells
J2 - Cells
PY - 2026
DA - 2026/08/11
VL - 15
IS - 16
SP - 1445
SN - 2073-4409
PB - Multidisciplinary Digital Publishing Institute (MDPI)
DO - 10.3390/cells15161445
UR - https://doi.org/10.3390/cells15161445
LA - en
ER -

CSL-JSON

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"author": [
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