Date of Award
2026
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. Chris Risher
Third Advisor
Dr. Louise Risher
Fourth Advisor
Dr. Swarup Mitra
Fifth Advisor
Dr. Daniel Morgan
Abstract
Nicotine use is a tremendous public health issue in the United States, with over 23 million people being dependent on the substance. Low cessation rates associated with nicotine use are largely attributed to the withdrawal and craving symptoms that occur after abstinence of use from nicotine. The medial habenula (MHb) and interpeduncular nucleus (IPN) are two brain regions heavily associated and linked with nicotine withdrawal. Here, I sought to understand how these brain regions are altered in their physiology during nicotine intake. Utilizing E-Vape self-administration, mice were first taught to selfadminister nicotine of various, clinically relevant, dosages which correlate to common refillable and disposable nicotine and flavorant concentrations. Following selfadministration, mice were assessed for alterations in neuronal physiology in the MHb and IPN utilizing whole-cell patch-clamp electrophysiology. Results from my studies have shown that, first, the male MHb is inherently more excitable than the MHb in females. Next, electrophysiological studies in the MHb demonstrated that the factors of sex, nicotine dosage, and flavorant presence all impacted excitability of the brain region when correlating excitability metrics to behavior. When assessing the IPN, and similar to the MHb, I again observed that the male IPN was inherently more excitable than the female counterpart. Interestingly, though none of the excitability metrics utilized in the MHb study yielded significant correlations when compared to behavior, I found that resting membrane potential (RMP) would become slightly less negative in the IPN as selfadministration behavior increased. Additionally, I observed that only a high dose of nicotine would decrease action potential output in the IPN in females, where in males, action potential output would decrease in a dose-dependent manner. These results point to a highly sexually dimorphic circuit contained in the brain that largely influences both nicotine intake and withdrawal.
Subject(s)
Neurosciences.
Nicotine.
Nucleus.
Public health.
Substance abuse.
Brain -- Physiology.
Neurophysiology.
Nicotine addiction.
Recommended Citation
Olszewski, Nathan Alexander, "Nicotine self-administration and the impacts on medial habenula and interpeduncular nucleus neurophysiology" (2026). Theses, Dissertations and Capstones. 2113.
https://mds.marshall.edu/etd/2113
