Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

Imad M. Damaj

Abstract

Although cigarette smoke has been implicated in a causal relationship with various types of cancers, around 62% of all cancer patients are current smokers, recent quitters, or former smokers. While most patients who are smokers are motivated to quit after cancer diagnosis, 25 -30% of these patients continue to smoke. Furthermore, most quitters relapse after 2-3 years of post-chemotherapy. This represents a major health concern since several clinical studies revealed that perpetuation of smoking in cancer populations attenuates patient's well-being and quality of life. Smoking may impair healing, attenuate the efficacy of chemotherapy, increase the disease complications and diminish survival rates. However, the factors that involved in nicotine dependence in cancer patients are poorly understood. xii According to human research, it was suggested that tumor site, impact of cancer therapy and disease prognosis could be responsible of continuation of tobacco smoking among cancer patients and survivors. Recently, chemotherapy was shown to cause emotional deficits in humans (anxiety, insomnia and depression) and animals. In this project, we focused on the chemotherapeutic agent, paclitaxel, because it is widely used to treat solid tumors such as lung, head, neck and breast cancer. We previously reported that paclitaxel induced general affective deficits in mice such as anhedonia, anxiety and depression-like behaviors. We therefore hypothesized that the chemotherapeutic agent, paclitaxel may alter the rewarding and withdrawal properties of nicotine. We investigated the impact of paclitaxel on spontaneous nicotine withdrawal and nicotine reward in C57BL/6J mice by using variety of behavioral tests. Our findings showed that paclitaxel worsened the somatic and affective signs of nicotine withdrawal in male mice as well as attenuated of nicotine reward in the CPP assay. These behavioral changes were not due to an impact of nicotine metabolism by paclitaxel. Overall, paclitaxel changed the behaviors during nicotine withdrawal and reward and that suggested changing in the smoking behavior after exposure to chemotherapy.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-14-2017

Available for download on Wednesday, December 07, 2022

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