Dissertations, Theses, and Capstone Projects

Date of Degree

9-2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Psychology

Advisor

Jeff Beeler

Committee Members

Carolyn Pytte

Richard Bodnar

Robert Ranaldi

Ewa Galaj

Subject Categories

Biological Psychology | Neuroscience and Neurobiology | Systems Neuroscience

Keywords

dopamine, nicotine, basal ganglia, midbrain, addiction, fiber photometry

Abstract

Tobacco is one of the most widely used substances across the United States; tobacco consumption is linked with several diseases and is one of the leading causes of preventable death in the country. Nicotine is the active substrate found in tobacco products, acting as a stimulant, which reinforces continued use. The introduction of tobacco-free options such as e-cigarettes and oral pouches has driven an increase in nicotine exposure across the population, especially in young adults. Acute nicotine use induces neuroadaptations in the mesolimbic dopaminergic system, which mediates reinforcement learning and addiction, that potentiates reward-related neurotransmission. Furthermore, there are clinical studies showing that continued nicotine use during treatment of Substance Use Disorders (SUDs) jeopardizes recovery and increases relapse rates during abstinence (Tsoh et al., 2019; Vlad et al., 2020). Although the effects of acute nicotine administration have been well established, there is limited research on the effects of long-term nicotine use. Our aim was to investigate how chronic nicotine (cNIC) exposure affects reinforcement learning using an optogenetic intracranial self-stimulation (oICSS) paradigm with two lever contingencies. We found that cNIC mice preferentially reinforce on the lower-cost lever in comparison to controls, and that this behavior was associated with attenuated dopamine and exaggerated cholinergic activity. We also found that the relationship between striatal dopamine and acetylcholine becomes dysregulated during reinforcement in cNIC mice. These results indicate a potential mechanism through which nicotine mediates reinforcement learning by creating a preference for certain stimuli through reward encoding. Future investigations should examine subunit specific receptor upregulation within the mesolimbic dopamine circuit, with the aim of informing potential treatment targets for nicotine and other substance co-use.

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