O'Dell, Laura E, PhD
Diabetes Enhances Susceptibility to the Rewarding Effects of Nicotine
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Clinical Therapeutics/New Technology, Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Complications, Insulin Action, Insulin Action\Insulin Resistance, Obesity, Obesity\Animal Models
Type of Grant: Basic Science
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Patients with diabetes have heath complications that are magnified by tobacco use. Despite this, diabetic subjects appear to be more vulnerable to tobacco abuse than the general population. An unanswered question is whether diabetic patients are more susceptible to tobacco abuse due to greater pleasurable effects of nicotine versus healthy controls. There is a fundamental gap in our understanding of how the brain of diabetic patients is more sensitive to the pleasurable effects of nicotine.
This proposal will examine whether the rewarding effects of nicotine are enhanced in diabetic rats using an animal model that allows the rat to perform lever presses for nicotine infusions. Preliminary data demonstrate that diabetic rats find nicotine more rewarding as compared to healthy controls. Furthermore, we learned that the biological mechanisms of this effect is related to reduced dopamine systems in a brain region that controls the pleasurable effects of nicotine. Thus, we hypothesize that enhanced susceptibility to tobacco abuse in diabetic persons is due to an overcompensation of suppressed dopamine systems. Our proposal will examine this hypothesis using two rodent models of diabetes involving insulin suppression or chronic high fat feeding. Subsequent studies will examine whether the effects of diabetes on nicotine intake and brain changes are returned to control levels following insulin replacement. This research is an important step towards elucidating the substrates mediating enhanced tobacco abuse in diabetic patients. Our findings will help guide the development of specialized treatments for diabetic patients that suffer from health complications exacerbated by tobacco abuse.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
The area of diabetes research that this project relates to is whether patients with diabetes have enhanced vulnerability to tobacco abuse. Patients with diabetes have heath complications that are magnified by tobacco use. Despite this, diabetic subjects appear to be more vulnerable to tobacco abuse than the general population. An unanswered question is whether diabetic patients are more susceptible to tobacco abuse due to greater pleasurable effects of nicotine versus healthy controls. There is a fundamental gap in our understanding of how the brain of diabetic patients is more sensitive to the pleasurable effects of nicotine. This proposal will examine whether the rewarding effects of nicotine are enhanced in diabetic subjects. Preliminary data demonstrate that diabetic subjects find nicotine more rewarding as compared to healthy controls. Furthermore, we learned that the biological mechanisms of this effect is related to suppressed dopamine systems in a brain region that mediates the pleasurable effects of nicotine. Thus, we hypothesize that enhanced susceptibility to tobacco abuse in diabetic persons is due to overcompensation for suppressed dopamine systems.
Our proposal will examine this hypothesis using two models of diabetes involving insulin suppression or chronic high-fat feeding. Subsequent studies will examine whether the effects of diabetes on nicotine intake and brain changes return to control levels following insulin replacement. This research is an important step towards elucidating the substrates mediating enhanced tobacco abuse in diabetic patients. Our results will provide important information towards understanding the role of dopamine systems in mediating enhanced vulnerability to tobacco abuse in diabetic patients. At the completion of the proposed studies, our findings will also speak to the potential clinical efficacy of pharmacotherapies that target dopamine systems. Our findings will help guide the development of specialized treatments for diabetic patients that suffer from health omplications exacerbated bytobacco abuse. Thus, this project will play an important role in advancing the mission of the ADA to improve the lives of diabetic persons, particularly those that are more inflicted by the health consequences of tobacco abuse.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
There are several ways in which the outcomes of this project will help persons with diabetes. If a person with diabetes asked how our project would help them in the future, we would give them a thoughtful and careful explanation that would include the following discussion points: First, the results of this project will inform whether patients with diabetes are more vulnerable to tobacco abuse. A disturbing epidemiological finding is that young persons with diabetes display smoking rates that are nearly double that of the general population. Therefore, knowledge regarding enhanced susceptibility to tobacco abuse in diabetic persons may inform educational and prevention strategies targeted at avoiding tobacco abuse in persons with diabetes. Second, the results of our project will inform whether glucose regulation via FDA approved medications reverses changes in brain systems that mediate enhanced vulnerability to tobacco abuse. These data will be an important first step towards understanding the role of insulin regulation in tobacco abuse liability. Third, the results of our project will examine the role of dopamine systems in tobacco abuse in diabetic subjects.
The results of these studies are important, as they will inform the development of smoking cessation treatments that target dopamine in patients with diabetes. As medicine moves towards more specialized treatment strategies, the development of medications that reduce tobacco use in diabetic patients is of utmost importance. Lastly, a better understanding of how diabetes influences dopamine systems is important because this neurotransmitter system modulates several mental (addiction, depression, schizophrenia, anxiety) and physical (Parkinson’s disease, motor dyskinesia) health conditions. A better understanding of how diabetes influences dopamine systems can also lead to a better understanding of the etiological basis for the co-occurrence of diabetes with other diseases.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
It is important for me to become involved in diabetes research for several reasons. First, the behavioral aspects of the project will be conducted in El Paso, which borders Juarez, Mexico. Unfortunately, diabetes is rampant in our border region and the rates of tobacco use are above national levels. Thus, everyday we observe the compounded health consequences of diabetes and tobacco use. Second, our research team has several family members inflicted with diabetes, including my father-in-law who died this year from complications associated with long-term diabetes. I also suffered from gestational diabetes and am of Mexican-American descent. Thus, my cultural background and personal experiences have fueled my desire to work towards preventing, curing, and helping persons with diabetes. Lastly, it is a pleasure to mentor students in a community where we can foster the development of minority scientists who are conducing research on a border-relevant issue, such as diabetes.
We appreciate the American Diabetes Association for their investment towards improving the lives of persons in our community. This award will have a major impact on my research efforts in many ways. First, my research program has focused on the neurobiology mediating enhanced vulnerability to tobacco abuse. Thus far, our work has focused on studying the biological underpinnings that lead to greater tobacco abuse in young persons and women. This project is a natural extension of our efforts towards understanding why certain populations are more vulnerable to tobacco abuse. Second, I am a member of the Neuroscience and Metabolic Disorders Unit of the Border Biomedical Research Center at UTEP This project will relate directly to our goal of studying the neuroscience of metabolic disorders that are prevalent in our border region. Lastly, this project will be conducted with Dr. Arbi Nazarian, a collaborating investigator at Western University of Pharmaceutical Sciences. This project will formalize a collaborative effort that will build upon our collective strengths in behavior and molecular biology.
In what direction do you see the future of diabetes research going?
Diabetes is becoming one of the most prevalent health issues of our time. Given the vast number of persons afflicted with diabetes, a better understanding of co-morbid conditions is of critical importance. Although the focus of this proposal is on tobacco addiction, there are other mental health conditions, such as depression, anxiety that patients with diabetes may also be more vulnerable to. A better understanding of how patients with diabetes are susceptible to these issues may lead to preventative and/or treatment strategies that improve the lives of persons living with diabetes. My interests in diabetes began when I saw a Neuroscience lecture on the distribution of insulin receptors in the brain. This led me to think about the manner in which changes in insulin levels might influence behavioral outcomes.
Recent theories in the field of addiction have suggested that all compulsive disorders such as overeating and drug taking are mediated by common neural substrates. Specifically, recent theories suggest that compulsive eating is mediated byovercompensation for suppressed dopamine systems in our brain reward pathways. Since dopamine plays a central role in mediating drug addiction, this led to our hypothesis that enhanced vulnerability to tobacco addiction in diabetic subjects may be related to suppressed dopamine systems. As a neuroscientist, I view diabetes as a disorder that produces a milieu of neurochemical changes that influence the central nervous system in a manner that changes many behavioral outputs. Thus, future studies might provide a better understanding of how diabetes affects the expression of mental health disorders and/or other disease states that are mediated by common neural pathways in the brain.
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