Date of Award


Degree Name

Biomedical Sciences


Joan C. Edwards School of Medicine

Type of Degree


Document Type


First Advisor

Dr. Brandon Henderson, Committee Chairperson

Second Advisor

Dr. Richard Egleton

Third Advisor

Dr. Lawrence Grover

Fourth Advisor

Dr. Chris Risher

Fifth Advisor

Dr. Mary-Louise Risher


Cigarette smoking remains the leading cause of preventable disease and death worldwide, with nearly half a million deaths per year in the United States alone. Of the 70% of adult smokers in the United States that desire to quit, only ~7% are successful. The long-standing use and dependence of these products, despite known health consequences, is primarily attributed to the nicotine-induced neurobiological and neurophysiological adaptations that take place during chronic use. Adolescent nicotine exposure alters the developing brain while also priming the brain for other drug addictions later in life. Though nicotine-induced reinforcement, nicotinic acetylcholine receptor (nAChR) upregulation, and enhanced dopamine neuron excitability have been discovered and studied over the past several decades, another key player in nicotine dependence is flavoring chemicals. Characterizing flavors other than menthol have been banned in combustible cigarettes, yet more than 15,000 flavor options remain available for electronic cigarette users. Electronic cigarettes, or electronic nicotine delivery systems (ENDS), were originally intended to provide a cleaner nicotine delivery system for chronic smokers, yet due to the enticing market of flavored products and the growing popularity of zero-nicotine flavored e-liquids among ENDS users, these devices exhibit an even greater concern than combustible cigarettes. With the new wave of nicotine users, especially those between the ages of 12 and 18, further studies need to be done to identify the mechanisms that flavor chemicals have on the dependence process and to contribute to future FDA regulations. This dissertation encompasses the investigations into popular green apple flavor chemicals and identifies their roles on reward and reinforcement in a vapor self-administration model with mice as well as their role in nAChR trafficking within cultured neuroblastoma-2a cells. Additionally, this work summarizes the effects of non-contingent vapor exposure, similar to human vaping patterns, on ex vivo nAChR expression, neuronal firing, and subsequent dopamine release in the ventral striatum of mice. These findings will provide insight into the neurological effects of persistent ENDS use in an attempt to combat the growing use of these products among the adolescent population.


Nicotine addiction – Research – United States.

Nicotinic receptors.

Electronic cigarettes – Health aspects.

Vaping – Health aspects.