Nicole M. Avena - US grants

DESCRIPTION (provided by applicant): The objectives and aims of this research proposal are to investigate the neural and behavioral correlates of sugar and drug addictions. The recent increased awareness of eating disorders and obesity in our country has led many to speculate about the addictive properties of food, and how this addiction may be related to the over-eating epidemic our society is currently facing. Recent research in rodents has indicated that sugar bingeing can lead to dependency that shares some behavioral and neurochemical similarities with drug dependency (Colantuoni et al., 2001; Colantuoni et al., 2002). This proposal plans to elaborate on these findings, by behaviorally investigating sugar craving, sensitization and cross-sensitization with other known drugs of abuse. Moreover, this research will examine neurochemical similarities between sugar and drug addiction in the nucleus accumbens. By further elucidating a possible link between food and drugs, new pharmacological and behavioral treatments may be developed to treat eating disorders.

[unreadable] DESCRIPTION (provided by applicant): Obesity currently poses a threat to public health in the industrialized nations and therefore is directly relevant to the mission of the NIMH to reduce the burden of behavioral disorders through research on the brain and behavior. It is also relevant to the mission of the NIDDK to study metabolic and endocrine disorders affecting public health using basic science. Binge eating of palatable foods is a behavioral characteristic of obesity and other eating disorders, making it of great clinical relevance and utmost importance to understand neural mechanisms underlying its behavior. Bingeing on palatable foods can induce behaviors and alterations in the brain that are similar to the effects of drugs of abuse; however, little is known about the neurochemical or molecular mechanisms underlying this phenomenon. The primary goal of this proposal is for me to learn and apply the techniques of in situ hybridization, immunohistochemistry, radioimmuno-assay and capillary electrophoresis to identify and characterize some common neural mechanisms underlying binge eating of palatable foods and drug use. This proposal will measure opioid and non-opioid peptide expression as well as amino acid release in areas of the brain that regulate both feeding behavior and drug dependence, namely, the lateral hypothalamus (LH) and nucleus accumbens (NAc). These analyses will be performed as a function of binge eating of palatable foods (fat vs. sugar) compared with ad libitum access to the food. In addition, measures of circulating levels of steroid hormones and lipids will be collected and related to these neurochemical changes in the brain. I propose to test the novel hypotheses that: 1) opioids and amino acids in the LH function in relation to the macronutrient content of a palatable food independent of access schedule, whereas in the NAc they function in relation to the binge eating resulting from intermittent access to a palatable food; 2) these brain regions and their respective functions are connected via a population of non-opioid, orexigenic peptide neurons in the LH that project to the NAc; 3) the circulating steroids and lipids, which are elevated by consumption of a palatable, high-fat diet, modulate the neurochemicals of the LH and NAc that contribute to the process of binge eating of fat- rich foods. This research will identify some neural and molecular mechanisms underlying binge eating associated with obesity, which is an important public health issue. Information about the processes in the brain underlying binge eating of fat-rich foods will be useful for developing treatments to reduce this behavior and ultimately the incidence of obesity. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): With obesity rates continuing to rise, new and different research approaches are needed to develop strategies to impede this trend. I have been using preclinical models to study the unique theory that overeating of palatable foods, in the form of binge eating, can resemble an "addiction" to food, with concomitant behaviors and neurochemical changes that are like those seen with drug addiction. These data and the findings of others support the theory that overeating of palatable food might produce an extreme motivation that resembles a dependency on certain foods, possibly fueling the urge to overeat and subsequent obesity in some individuals. As it is imperative to test whether animal models of overeating are clinically reliable, in this proposal I plan to obtain clinical research training so that I can study and refine psychometric methods to assess "food addiction" in clinical patients who are obese or have binge eating disorder. Further, I plan to take the next step in my preclinical research by obtaining data on the effect that overeating can have on the expression of genes that are known to have roles in addiction, and to understand how overeating on different types of nutrients (i.e., fat vs. sugar) can affect related brain systems and subsequent behavior. I have an aggregate skill set that will be further developed in this proposal, which will enable me to complete these studies and facilitate my development as an independent research scientist. I have a Ph.D. in Psychology and Neuroscience from Princeton University and postdoctoral experience in molecular biology from The Rockefeller University. I am now Assistant Research Professor at University of Florida, College of Medicine, Department of Psychiatry. My research studies up to this point have focused on using my skills in behavioral neuroscience and molecular biology to study of "food addiction," in part, through the use of an animal model of sugar dependence that I developed in my Ph.D. research. This research has resulted in 33 publications, many speaking invitations and presentations, and several awards. Further, I have a track record of obtaining funding through individual predoctoral and postdoctoral NIH NRSA awards, and small private foundations. Recognizing the importance and usefulness of translational research, I now plan to expand my research skills by obtaining additional training in clinical science. This will allow me to relate my preclinical studies of overeating to clinical populations, and this will help to provide further validity to the theory of "food addiction." This proposal outlines a series of career development activities that will be conducted within the context of translational research on overeating palatable foods and the possible ensuing development of "food addiction." The research and career development activities will occur at the University of Florida, College of Medicine, Department of Psychiatry, which is an ideal place for this training to take place. Not only are there several researchers in the Addition Medicine division of the Department of Psychiatry who are interested in studying "natural addictions," but there are also resources and individuals throughout the University of Florida that will be an asset to this research project and my development as an independent scientist. A team of mentors has been assembled to guide me through this development phase, each with a unique contribution to the proposed training and research elements. In addition, I have identified collaborators that will contribute their expertise and knowledge to the proposed experiments. Career development plans include advanced coursework in clinical research, epidemiology and statistics, as well as participation in scientific organizations, attendance to lectures and seminars, and training in the responsible conduct of research. The research training will focus on developing my skills as a clinical researcher so I can conduct translational research on overeating and abnormal food intake. In the long term, I hope to have my own teaching and research laboratory in which I can continue to conduct research on the neurobiology of aberrant feeding behavior using both preclinical and clinical models. The proposed experiments are centered on developing a translational line of inquiry. Aim 1 will employ clinical research practices and psychometrics to modify and implement the Yale Food Addiction Scale in obese and binge eating disorder patients and normal controls to 1) determine if patients in these clinical populations show signs of "food addiction" using this scale, and 2) relate food preference to the addiction-like behaviors using newly-developed subscales. Further, to inform and expand on these findings, Aim 2 is a preclinical research component that will assess differences in behaviors and gene expression in reward-related brain areas that result from overeating fat vs. sugar using established animal models. Aim 2 will use behavioral measures and molecular biological techniques in rodent models of overeating. This translational approach to research will permit a better understanding of various aspects of overeating and inform the development of future models to investigate the biological basis of aberrant feeding behavior, which may then be applied to studies in clinical populations. At the end of this training, I will be able to launch a career as an independent investigator and be poised to develop a comprehensive, programmatic translational research program.