Nicotine self-administration suppresses both pro- and anti-inflammatory accumbens cytokines but does not induce apoptosis in female rats

Authors

• Ashley M. White, University of Kentucky College of MedicineFollow
• Daryl L. Richie, University of Kentucky College of MedicineFollow
• Percell T. Kendrick, University of Kentucky College of MedicineFollow
• Kathleen R. McNealy, University of Kentucky College of MedicineFollow
• Robert M. Flight, University of Kentucky College of MedicineFollow
• Hunter N.B. Moseley, University of KentuckyFollow
• Christa L. Corley, University of Kentucky College of MedicineFollow
• Cassandra D. Gipson, University of KentuckyFollow

Abstract

Nicotine can alter neuroimmune signaling within the brain reward pathway, and specifically, within the nucleus accumbens (NAc). Despite clinically meaningful sex differences in nicotine use as well as known sex differences in immune system function, no studies have evaluated NAc neuroimmune consequences following nicotine use in females. Thus, the present study evaluated cytokine expression and neuronal apoptosis in the ventral striatum (which encompasses the NAc) in ovary-intact female Long-Evans rats following nicotine or saline self-administration. Circulating cytokine levels were also evaluated in serum. Overall, pro-inflammatory cytokine levels were suppressed within the ventral striatum, with tumor necrosis factor-alpha (TNFα) being the most significantly suppressed. Interestingly, there was an increase in the chemokine fractalkine (FKN), a neuronal “help me” signal during distress. These results raise the possibility that chronic volitional nicotine use results in cleavage of FKN in response to neuronal distress, and glial cells may be unresponsive to these signals. In contrast, circulating serum cytokine levels remained mostly unchanged except for an increase in TNFα, suggesting that the immunosuppression observed following nicotine self-administration was largely localized to the brain. No measurable NAc apoptotic debris was identified, in line with our findings that interleukin-1β (IL-1β) was suppressed and raising the possibility that nicotine use suppresses NAc inflammasome activation. Thus, chronic nicotine use in female rats may disrupt ventral striatal neuroimmune homeostasis. Together, targeting nicotine-induced disruptions in neuroimmune homeostasis may represent novel therapeutic opportunities to mitigate the harmful effects of nicotine in females.

Document Type

Article

Publication Date

9-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s).

Digital Object Identifier (DOI)

10.1016/j.addicn.2026.100263

Archival?

Archival

Repository Citation

White, Ashley M.; Richie, Daryl L.; Kendrick, Percell T.; McNealy, Kathleen R.; Flight, Robert M.; Moseley, Hunter N.B.; Corley, Christa L.; and Gipson, Cassandra D., "Nicotine self-administration suppresses both pro- and anti-inflammatory accumbens cytokines but does not induce apoptosis in female rats" (2026). Psychology Faculty Publications. 269.
https://uknowledge.uky.edu/psychology_facpub/269