2007 — 2013 |
O'dell, Laura Elena |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Nico-Teen: Mechanisms of Nicotine Reward and Withdrawal During Adolescence @ University of Texas El Paso
[unreadable] DESCRIPTION (provided by applicant): Tobacco abuse among adolescents is a major health and economic concern, yet there is a critical knowledge gap regarding the mechanisms that mediate adolescent smoking behavior. Our preliminary data demonstrate that adolescent male rats display enhanced nicotine reward and reduced nicotine withdrawal relative to adults. This proposal extends our previous work by examining the neural mechanisms that mediate developmental sensitivity and sex differences in the behavioral .effects of nicotine reward and withdrawal. In order to study the long-term consequences produced by adolescent nicotine exposure, our proposal also includes adult rats pre-exposed to nicotine during adolescence. Nicotine reward is mediated in part by enhanced dopamine (DA) transmission in the nucleus accumbens (NAcc). In contrast, nicotine withdrawal produces a decrease in NAcc DA levels. Changes in NAcc DA transmission are mediated by excitatory and inhibitory systems that regulate DA projections that originate in the ventral tegmental area (VTA). During adolescence, excitatory systems that regulate DA are overdeveloped, whereas inhibitory systems are underdeveloped. We hypothesize that adolescents will display enhanced nicotine reward and reduced nicotine withdrawal relative to adults. These developmental differences are likely mediated via enhanced excitation and reduced inhibition of VTA DA cell bodies. Overall we expect that these differences will be magnified in female adolescents and nicotine pre-exposed rats. This is based on clinical studies demonstrating that teenage females and adults pre-exposed to nicotine during adolescence display enhanced vulnerability to long-term tobacco abuse. Behavioral studies will compare nicotine reward using place preference procedures and nicotine withdrawal using place aversion procedures. Neurochemical studies will employ in vivo microdialysis procedures to compare NAcc DA and concomitant measures of excitatory and inhibitory systems in the VTA following nicotine administration and during nicotine withdrawal. This research is significant because our findings may have significant implications towards guiding public policies regarding tobacco regulation and warnings directed at teenagers and females. Further, a better understanding of the mechanisms mediating adolescent tobacco abuse will lead to more effective treatments for young smokers who are most at risk of developing diseases caused by long-term smoking. [unreadable] [unreadable] [unreadable]
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2012 — 2016 |
Echegoyen, Lourdes Miranda-Arango, Manuel (co-PI) [⬀] O'dell, Laura Elena |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Summer Mentoring and Research Training: Methods in Neuroscience of Drug-Abuse @ University of Texas El Paso
DESCRIPTION (provided by applicant): The SMART-MIND project (Summer Mentoring and Research Training: Methods in Neuroscience of Drug-abuse), to be conducted at the University of Texas at El Paso (UTEP), is directed at enriching the science education and research training of 8 undergraduate students and 2 high school teacher-student teams (TST) with a specific focus on the neuroscience of drug-addiction. The program will provide a high quality experience that combines education, novel research in state-of-the-art facilities, training in bioethics, one-on-one and group mentoring, and training in several relevant professional skills. Participants will be immersed in research projects directed by a group of eight neuroscientists in the departments of biological sciences, psychology and chemistry, who have established and funded collaborations among themselves. The various projects center around biological, behavioral, biochemical and molecular factors that contribute to addiction and the biochemical pathways leading to neurodegeneration, and its effect on other important aspects of the addiction process, such as behavioral plasticity, learning and memory. The program cohort of participants will consist of eight undergraduate students, and two high school teachers-student teams (TST). High school teachers and their students will be recruited from the El Paso Independent School District (EPSID). Four of the undergraduates will be UTEP students majoring in biological sciences, psychology, chemistry or science education. The other four undergraduates will be recruited primarily from El Paso Community College (EPCC) and institutions outside El Paso that are minority-serving or feature demographics with large numbers of underrepresented students. Given the nature of UTEP's location and demographics combined with a carefully planned involvement of participants from other institutions, the intended impact will extend much beyond El Paso. Specifically, this program aims at 1. Enticing and enabling more undergraduate students from UTEP, El Paso Community College (EPCC) and other minority serving institutions to pursue advanced degrees in neuroscience and related fields. 2. Increase the number of high school teachers in the El Paso region with research skills in and knowledge of neuroscience. 3. Increase the number of underrepresented minority high school students pursuing degrees and careers in science.
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2014 — 2018 |
O'dell, Laura Elena |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Sex Differences in the Mechanisms That Promote Nicotine Reward and Withdrawal @ University of Texas El Paso
DESCRIPTION (provided by applicant): Tobacco use remains a major public health and economic concern, particularly in women who are more vulnerable to the long-term health consequences of smoking than men. Despite the magnitude of the problem, there is a fundamental knowledge gap in our understanding of the mechanisms that promote tobacco use in females. If this knowledge gap is not filled, then reducing tobacco use and developing specialized medications for female smokers will remain largely incomprehensible. The long-term goal of our research program is to identify the mechanisms that mediate tobacco use among different clinical populations that are uniquely susceptible to this problem. The objective of this renewal is to determine the neural mechanisms that promote tobacco use in females. The central hypothesis is that females are more susceptible to tobacco use than males because of stronger rewarding effects of nicotine and heightened anxiety produced by withdrawal from this drug. Our mechanistic hypothesis is that estradiol (E2) promotes the rewarding effects of nicotine and magnifies the stress produced by nicotine withdrawal in females. More specifically, we postulate that sex differences in response to nicotine are modulated within the neural circuits of the nucleus accumbens (NAcc), where dopamine is increased following nicotine administration and decreased during withdrawal from this drug. Thus, females experience greater rewarding effects of nicotine in the presence of E2, which promotes dopamine release in the NAcc. Following repeated nicotine exposure, opponent processes develop to counteract the chronic over-activation of dopamine release. We suggest that the emergence of these opponent processes is evident during withdrawal from chronic nicotine as an increase in the stress hormone, corticotropin releasing factor (CRF) in the NAcc. This increase in CRF levels enhances the inhibitory tone in the NAcc, which results in a decrease in dopamine release during nicotine withdrawal. Thus, females experience greater anxiety during nicotine withdrawal in the presence of E2, which promotes the recruitment of opponent stress systems that suppress dopamine release in the NAcc. The proposed studies reflect a multi- disciplinary approach involving neurochemical, behavioral, and gene transfer techniques to compare sex differences in the rewarding effects of nicotine (Aim 1) and the aversive states produced by withdrawal (Aim 2) because both of these factors are believed to promote tobacco use in females. The approach to studying sex differences involves comparisons of male, female, and OVX female rats. If the removal of ovarian hormones reverses the proposed measures in females, then the role of E2 will be assessed in OVX rats that will receive E2 supplementation and will be tested following E2 or vehicle administration. At the completion of this project, our findings will help us develop a unifying hypothesis regarding the factors that promote tobacco use in females. This exemplifies the significance of this research because a better understanding of the mechanisms that fuel tobacco use in females will lead to more effective treatments to reduce health disparities in women.
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2017 — 2018 |
Diaz-Martinez, Laura Angelica (co-PI) [⬀] Miranda-Arango, Manuel (co-PI) [⬀] O'dell, Laura Elena |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Summer Mentoring and Research Training: Methods in Neuroscience of Drug-Abuse (Smart-Mind) @ University of Texas El Paso
ABSTRACT This is a renewal application of the SMART-MIND Program (Summer Mentoring and Research Training: Methods In Neuroscience of Drug-abuse), to be conducted at the University of Texas at El Paso (UTEP). During the original funding period, we provided an intensive summer training experience for 46 undergraduates and 10 high school teacher-student teams from diverse backgrounds. Our overarching goal is to provide a streamlined and effective training experience that increases knowledge and research skills in neuroscience and drug abuse. In the next period, our goal is to continue to enrich the science education and research training of undergraduates and high school teacher-student teams each summer with a continued focus on neuroscience and drug addiction. The program will combine education, innovative research in state-of-the-art facilities, training in bioethics, one-on-one and group mentoring, and professional development. Participants will be immersed in research projects directed by a multi-disciplinary group of 12 neuroscientists with established and funded interdisciplinary collaborations among themselves. The projects center around behavioral and biological factors that contribute to addiction and the biochemical pathways leading to neurodegeneration, behavioral plasticity, learning and memory. Each cohort will consist of 8 undergraduates and 2 high school student-teacher teams. High school teachers will be guided in the development of novel curricula, didactic seminars in science education, and various outreach activities that will foster implementation of the learning objectives in their home high schools. Four of the undergraduates will be local UTEP or community college students majoring in neuroscience-related fields and the other 4 undergraduates will be recruited from outside El Paso with a focus on minority-serving institutions. This will increase the reach of the program outside of the El Paso region while continuing our focus on promoting involvement of underrepresented minorities in biomedical research. Specifically, this program aims at: 1) Enticing and enabling an increasing number of undergraduate students from UTEP, El Paso Community College (EPCC) and other minority serving institutions to pursue advanced degrees in neuroscience and related fields 2) Increase the number of high school teachers in the El Paso region with research skills in and knowledge of neuroscience and 3) Increase the number of underrepresented minority high school students pursuing degrees and careers in science.
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