Date of Award

2025

Degree Name

Biomedical Research

College

Joan C. Edwards School of Medicine

Type of Degree

Ph.D.

Document Type

Dissertation

First Advisor

Dr. Brandon Henderson

Second Advisor

Dr. Mary-Louise Risher

Third Advisor

Dr. Cynthia Jones

Fourth Advisor

Dr. Chris Risher

Fifth Advisor

Dr. Swarup Mitra

Abstract

Smoking is a major public health concern. Despite decades of accumulated evidence of the negative health consequences, smoking remains the leading cause of preventable death in the United States, with about 500,000 deaths each year. Whereas the use of combustible cigarettes has declined in the United States, the use of electronic nicotine delivery systems (ENDS) has increased drastically. Nicotine, the psychoactive ingredient in tobacco and ENDS products, has been shown to induce its reinforcing properties by directly activating dopaminergic, GABAergic, and glutamatergic neurons within the ventral tegmental area. It is well-documented that the activation of the ventral tegmental area by nicotine stimulates the release of dopamine, which projects to the nucleus accumbens and the prefrontal cortex. In addition to its neurophysiological complications, the usage of nicotine-containing products is associated with chronic diseases such as respiratory and cardiovascular diseases, cancers, and diabetes. The surge in the mortality rate and comorbidities associated with smoking has prompted efforts to identify factors that enhance nicotine abuse liability. One of the factors currently under investigation is obesity-inducing diets (e.g. high-fat and high-sugar diets). Preliminary findings suggest that excessive consumption of obesity-inducing diets could cause neuroadaptive changes in the reward pathway, potentially influencing drug use. Despite this knowledge, few studies have examined the exact neurochemical mechanisms mediating high-fat diet-induced obesity and nicotine addiction in preclinical models. To address this limitation, Chapters 1 and 2 of this dissertation review the neurobiological properties of nicotine and obesity through the lens of the dopamine reward pathway. In Chapter 3, we examine the influence of high-fat diet on nicotine reinforcement- and motivation-related behavior in a model system that mimics human vaping. In Chapter 4, we explore the synergistic effects of obesogenic diet and vaporized nicotine exposure on ventral tegmental area dopamine physiology, cell integrity, and metabolic health in adult mice. Additionally, this dissertation investigates whether nicotine doses and/or popular flavoring additives found in nicotine-containing products mediate vaping-related behaviors in diet-induced obese adult mice. With the rise in fast-food culture and the continued high numbers of smoking-related deaths, these findings offer an insight into the exact mechanisms modulating comorbid conditions such as obesity and smoking (including vaping).

Subject(s)

Neurosciences.

Social sciences.

Pharmacology.

Dopamine.

Glucose.

Nicotine.

Diet.

Obesity.

Public health.

Smoking.

Electronic cigarettes.

Vaping.

Download

Available for download on Tuesday, November 17, 2026

Share

COinS