After noticing the spectrum of successes and failures that accompany smoking cessation, Emily Eshraghian developed a keen interest in the mechanisms of addiction, relapse, and withdrawal. Her curiosity led her to join Professor Leslie's lab, where she could explore the mechanistic differences of cigarette smoke cessation versus nicotine cessation. She particularly appreciates how her work has contributed to her growth as a student, researcher, and public health advocate; it has challenged her to think critically about scientific inquiries, while remaining receptive to the novelty required in research and medicine. After graduation, Emily will pursue her Master of Public Health in Epidemiology and aims to attend medical school.

Tobacco addiction is a chronic relapsing condition with negative impacts on public health. Nicotine is widely accepted to be the primary addictive component in tobacco; yet, current cessation therapies are ineffective. Many such therapies target α4β2 and α7 nicotinic acetylcholine receptors (nAChRs). However, other tobacco constituents also play a role. Studies have shown that α3β4 nAChRs function in nicotine dependence and provide a potential new target for smoking cessation. However, the role of α3β4 in drug-primed reinstatement (DPR) is still unclear. Here, AT-1001, an α3β4 antagonist, was used to examine its efficacy in attenuating DPR of a solution containing nicotine and the aqueous components of tobacco, cigarette smoke extract, (CSE)- or nicotine-seeking in rats. Animals self-administered CSE or nicotine for 10 days minimum before being extinguished from drug-taking behavior. Upon extinction, animals were treated with AT-1001, followed by a priming dose of CSE or nicotine prior to reinstatement testing. The study found that AT-1001 attenuated DPR of CSE- and nicotine-seeking in a dose-dependent manner, with lower efficacy in CSE animals. This demonstrates that α3β4 in part mediates DPR, which supports the evidence that the inclusion of tobacco constituents enhances craving. This highlights the importance of including tobacco constituents in preclinical models.

Frances M. Leslie School of Medicine

This study shows that there is a difference in the mechanisms underlying craving following intake of nicotine alone and cigarette smoke extract. This is important because many teenagers and young adults are exposed to nicotine alone through e-cigarette use, rather than smoking cigarettes. The differences identified in the underlying pharmacological mechanisms may lead to new therapies for treatment of addiction caused by e-cigarette use. Emily’s work shows the value of doing faculty-mentored undergraduate research. It teaches students to carefully design and conduct studies that can be of clinical impact.