Alcohol self-administration and nicotine withdrawal alter biomarkers of stress and inflammation and prefrontal cortex changes in Gβ subunits

ABSTRACT

Background: Although alcohol and nicotine are often used together, the biological consequences of these substances are not well understood. Identifying shared targets will inform cessation pharmacotherapies and provide a deeper understanding of how co-use of alcohol and nicotine impacts health, including biomarkers of stress and inflammation.

Objective: We examined the effects of nicotine exposure and withdrawal on alcohol self-administration (SA), stress and inflammatory biomarkers, and a G-protein coupled receptor subunit (Gβ) in brain areas associated with drug use.

Methods: Male rats were trained to SA alcohol and then received a nicotine pump (n = 7–8 per group). We assessed alcohol intake for 12 days during nicotine exposure and then following pump removal to elicit withdrawal. After the behavioral studies, we assessed plasma leptin, corticosterone, and interleukin-1β (IL-1β), and Gβ protein expression in the amygdala, nucleus accumbens (NAc), and prefrontal cortex (PFC).

Results: Nicotine exposure or withdrawal did not alter alcohol intake (p > .05). Alcohol and nicotine withdrawal elevated corticosterone levels (p = .015) and decreased Gβ levels in the PFC (p = .004). In the absence of nicotine, alcohol SA suppressed IL-1β levels (p = .039). Chronic exposure to nicotine or withdrawal during alcohol SA did not alter leptin levels or Gβ expression in the amygdala or NAc (p’s > .05).

Conclusions: The combination of alcohol SA and nicotine withdrawal produced a persistent increase in stress biomarkers and a suppression in Gβ expression in the PFC, providing an important first step toward understanding the common biological mechanisms of alcohol/nicotine misuse.

KEYWORDS:

• alcohol
• nicotine
• withdrawal
• stress
• inflammation
• immune
• biomarkers
• Gβ Signaling
• comorbidity

Acknowledgments

BC, CAH, MA, KC, RCG, RJF performed the experiments. BC and CTS performed the Luminex procedures. MA, KC, RCG, SR performed western blot experiments. BC, BSG, and LEO conducted the statistical analyses, interpretation of data, and prepared original drafts of this manuscript. BSG, VV, and MR provided critical feedback on the framing and interpretation of this work. All authors reviewed, edited, and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by NIDA grants DA021274 and DA033613 to LEO. This work was also supported by NIMHD grant G12MD007592 that provided a pilot project award through the Border Biomedical Research Center at UTEP for SR and LEO as well as a supplement award to LEO through U54MD007592. BC was supported on T32 AA007456 from NIAAA. This work was also supported by a grant from the El Paso Community Foundation from the Stern Family Foundation awarded to LEO and BG. These funding agencies had no direct involvement in the study design, data interpretation, or the decision to submit this article for publication.