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- Creators: Arizona State University
- Creators: Department of Supply Chain Management
- Member of: Theses and Dissertations
Description
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of this study is to investigate the literacy practices of three members of Alcoholics Anonymous (A.A.) and to explore how they use these practices to support and maintain their recovery in their lives. This study also aims to examine how each participant used specialist language, enacted certain identities and acquired the secondary Discourse in A.A. through literacy use. This dissertation study is the result of in-depth interviewing in which each participant was interviewed three times for 90-minutes. These interviews were then transcribed and analyzed using discourse analysis. Study results are presented in three chapters, each one designated to one of the participants. Within these chapters is a life history (chronology) of the participant leading up to the point in which they got sober. The chapters also include a thematic discourse analysis of the interview transcripts across themes of literacy practice and topics in A.A. A conclusion is then presented to investigate how literacy was used from a sociocultural perspective in the study. Due to the emotionally charged nature of this dissertation, it has been formatted to present the stories of the participants first, leaving the theoretical framework, literature review and research methods to be included as appendices to the main text.
ContributorsClausen, Jennifer Ann (Author) / Marsh, Josephine (Thesis advisor) / Hayes, Elisabeth (Committee member) / Serafini, Frank (Committee member) / Arizona State University (Publisher)
Created2013
Description
A variety of studies have shown that the tendency toward nicotine dependence has a genetic component. The work described in this thesis addresses three separate questions: i) are there unidentified SNPs in the nicotinic receptors or other genes that contribute to the risk for nicotine dependence; ii) is there evidence of ongoing selection at nicotinic receptor loci; and, iii) since nicotine dependence is unlikely to be the phenotype undergoing selection, is a positive effect on memory or cognition the selected phenotype. I first undertook a genome –wide association scan of imputed data using samples from the Collaborative Study of the Genetics of Nicotine Dependence (COGEND). A novel association was found between nicotine dependence and SNPs at 13q31. The genes at this newly associated locus on chromosome 13 encode a group of micro-RNAs and a member of the glypican gene family. These are among the first findings to implicate a non-candidate gene in risk for nicotine dependence. I applied several complimentary methods to sequence data from the 1000 Genomes Project to test for evidence of selection at the nicotinic receptor loci. I found strong evidence for selection for alleles in the nicotinic receptor cluster on chromosome 8 that confer risk of nicotine dependence. I then used the dataset from the Collaborative Studies on the Genetics of Alcoholism (COGA) and looked for an association between neuropsychological phenotypes and SNPs conferring risk of nicotine dependence. One SNP passed multiple test correction for association with WAIS digit symbol score. This SNP is not itself associated with nicotine dependence but is in reasonable (r 2 = 0.75) LD with SNPs that are associated with nicotine dependence. These data suggest at best, a weak correlation between nicotine dependence and any of the tested cognitive phenotypes. Given the reproducible finding of an inverse relationship between SNPs associated with risk for nicotine dependence and cocaine dependence, I hypothesize that the apparently detrimental phenotype of nicotine dependence may confer decreased risk for cocaine dependence. As cocaine use impairs the positive rewards associated with social interactions, reducing the risk of cocaine addiction may be beneficial to both the individual and the group.
ContributorsSadler, Brooke (Author) / Hurtado, Ana Magdalena (Thesis advisor) / Goate, Alison (Thesis advisor) / Hill, Kim (Committee member) / Nagoshi, Craig (Committee member) / Arizona State University (Publisher)
Created2014
Description
The current model of revenue generation for some free to play video games is preventing the companies controlling them from growing, but with a few changes in approach these issues could be alleviated. A new style of video games, called a MOBA (Massive Online Battle Arena) has emerged in the past few years bringing with it a new style of generating wealth. Contrary to past gaming models, where users must either purchase the game outright, view advertisements, or purchase items to gain a competitive advantage, MOBAs require no payment of any kind. These are free to play computer games that provides users with all the tools necessary to compete with anyone free of charge; no advantages can be purchased in this game. This leaves the only way for users to provide money to the company through optional purchases of purely aesthetic items, only to be purchased if the buyer wishes to see their character in a different set of attire. The genre’s best in show—called League of Legends, or LOL—has spearheaded this method of revenue-generation. Fortunately for LOL, its level of popularity has reached levels never seen in video games: the world championships had more viewers than game 7 of the NBA Finals (Dorsey). The player base alone is enough to keep the company afloat currently, but the fact that they only convert 3.75% of the players into revenue is alarming. Each player brings the company an average of $1.32, or 30% of what some other free to play games earn per user (Comparing MMO). It is this low per player income that has caused Riot Games, the developer of LOL, to state that their e-sports division is not currently profitable. To resolve this issue, LOL must take on a more aggressive marketing plan. Advertisements for the NBA Finals cost $460,000 for 30 seconds, and LOL should aim for ads in this range (Lombardo). With an average of 3 million people logged on at any time, 90% of the players being male and 85% being between the ages of 16 and 30, advertising via this game would appeal to many companies, making a deal easy to strike (LOL infographic 2012). The idea also appeals to players: 81% of players surveyed said that an advertisement on the client that allows for the option to place an order would improve or not impact their experience. Moving forward with this, the gaming client would be updated to contain both an option to order pizza and an advertisement for Mountain Dew. This type of advertising was determined based on community responses through a sequence of survey questions. These small adjustments to the game would allow LOL to generate enough income for Riot Games to expand into other areas of the e-sports industry.
ContributorsSeip, Patrick (Co-author) / Zhao, BoNing (Co-author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Sandra Day O'Connor College of Law (Contributor) / Department of Economics (Contributor) / Department of Supply Chain Management (Contributor)
Created2015-05
Description
While not officially recognized as an addictive activity by the Diagnostic and Statistical Manual of Mental Disorders, video game addiction has well-documented resources pointing to its effects on physiological and mental health for both addict and those close to the addict. With the rise of eSports, treating video game addiction has become trickier as a passionate and growing fan base begins to act as a culture not unlike traditional sporting. These concerns call for a better understanding of what constitutes a harmful addiction to video games as its heavy practice becomes more financially viable and accepted into mainstream culture.
ContributorsGohil, Abhishek Bhagirathsinh (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Computer Science and Engineering Program (Contributor)
Created2015-05
Description
This paper goes through a two-pronged approach in the attempt to understand E-Sports, entertainment gaming, and the creation of the E-Sports bar/Barcade. The first portion aims to explain and quantify the growth of electronic sports (or E-sports). This new craze has been growing immensely in the past 5 years, by viewership and by monetary endorsements. With these changes and growth patterns, we then move on to explain one of the many niche markets that has been created from the growth of E-sports and entertainment gaming. Through our experience in the field, we have evaluated 8 E-sports bars and Barcades in order to confirm their viability in the marketplace. Through our worldwide research we have found that E-sports will continue to grow and that Barcades will not only be viable, but will be a competitive market in the next 10-20 years.
ContributorsNist, Nicholas (Co-author) / Hester, James (Co-author) / Brooks, Dan (Thesis director) / Forss, Brennan (Committee member) / Barrett, The Honors College (Contributor) / Department of Economics (Contributor) / Department of Supply Chain Management (Contributor) / W. P. Carey School of Business (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
This thesis consisted in taking the preliminary steps in starting a business. Teamed up with a seasoned entrepreneur, we created a thorough Business Plan, Pro Forma and Investor presentation documents, all of which have been and still are being used in the process of creating the business. The business is in the competitive eSports industry, and involved camps and leagues targeted to youth ages 8-15. We have launched the first camp, and are in talks with investors and key strategic partners.
ContributorsHeiler, George (Co-author) / Gaynor, Tristan (Co-author) / Murphy, Kevin (Co-author) / Neck, Christopher (Thesis director) / McLurg, Dave (Committee member) / Department of Information Systems (Contributor) / Department of Supply Chain Management (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This dissertation explores the historical development and contemporary deployment of discursive practices that constitute the “truth” of addiction, which in turn serve as the bases for interventions into the lives of people who use intoxicants for any number of reasons. A number of interrelated research questions structure this governmentality analysis. First, what is the evolution of the governmental frames developed and deployed to understand, discipline, and recover addiction in the arena of alcohol and illicit drug use in United States? Second, how does twelve-step serve to transform unruly addicts into self-disciplining citizens? Finally, how does The Meth Project (TMP) exemplify and/or diverge from the dominant addiction governmental frames developed during the Temperance and Progressive eras in the United States? My overall goal is to destabilize our ready understanding of addiction and demonstrate that it is as much a tool of social needs as it is a mental illness by demonstrating: 1) the historically contingent nature of our understandings of addiction and addicts; 2) how these historically contingent understandings are actualized as technologies geared toward “recovering” unruly subjects; and 3) how these historically contingent understandings are taken up as “epistemological scripts” used to conceptualize the “true nature” of certain types of drugs and drug users while simultaneously supporting various regimes of discipline and punishment for those determined to remain “unruly subjects.”
ContributorsWalker, Michael F (Author) / Nadesan, Majia H (Thesis advisor) / Provine, Doris M (Thesis advisor) / Cavender, Gray (Committee member) / Brouwer, Daniel C (Committee member) / Arizona State University (Publisher)
Created2016
Description
The ability to manipulate the interaction between small molecules and biological macromolecules towards the study of disease pathogenesis has become a very important part of research towards treatment options for various diseases. The work described here shows both the use of DNA oligonucleotides as carriers for a nicotine hapten small molecule, and the use of microsomes to study the stability of compounds derived to treat mitochondrial diseases.
Nicotine addiction is a worldwide epidemic because nicotine is one of the most widely used addictive substances. It is linked to early death, typically in the form of heart or lung disease. A new vaccine conjugate against nicotine held within a DNA tetrahedron delivery system has been studied. For this purpose, several strands of DNA, conjugated with a modified dTpT having three or six carbon atom alkynyl linkers, have been synthesized. These strands have later been conjugated to three separate hapten small molecules to analyze which conjugates formed would be optimal for further testing in vivo.
Mitochondrial diseases are hard to treat, given that there are so many different variations to treat. There is no one compound that can treat all mitochondrial and neurodegenerative diseases; however, improvements can be made to compounds currently under study to improve the conditions of those afflicted. A significant issue leading to compounds failing in clinical trials is insufficient metabolic stability. Many compounds have good biological activity, but once introduced to an animal, are not stable enough to have any effect. Here, several synthesized compounds have been evaluated for metabolic stability, and several showed improved stability, while maintaining biological activity.
Nicotine addiction is a worldwide epidemic because nicotine is one of the most widely used addictive substances. It is linked to early death, typically in the form of heart or lung disease. A new vaccine conjugate against nicotine held within a DNA tetrahedron delivery system has been studied. For this purpose, several strands of DNA, conjugated with a modified dTpT having three or six carbon atom alkynyl linkers, have been synthesized. These strands have later been conjugated to three separate hapten small molecules to analyze which conjugates formed would be optimal for further testing in vivo.
Mitochondrial diseases are hard to treat, given that there are so many different variations to treat. There is no one compound that can treat all mitochondrial and neurodegenerative diseases; however, improvements can be made to compounds currently under study to improve the conditions of those afflicted. A significant issue leading to compounds failing in clinical trials is insufficient metabolic stability. Many compounds have good biological activity, but once introduced to an animal, are not stable enough to have any effect. Here, several synthesized compounds have been evaluated for metabolic stability, and several showed improved stability, while maintaining biological activity.
ContributorsSchmierer, Margaret (Author) / Hecht, Sidney M. (Thesis advisor) / Allen, James (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2016
Description
Serotonin 1B receptors (5-HT1BRs) are a novel target for developing pharmacological therapies to reduce psychostimulant craving. 5-HT1BRs are expressed in the mesolimbic pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), which is involved in reward and motivation. 5-HT1BR agonists modulate both cocaine- and methamphetamine-seeking behaviors in rat models of psychostimulant craving. In this dissertation, I tested the central hypothesis that 5-HT1BRs regulate cocaine and methamphetamine stimulant and rewarding effects in mice. I injected mice daily with cocaine for 20 days and then tested them 20 days after their last injection. The results showed that the 5-HT1BR agonist CP94253 attenuated sensitization of cocaine-induced locomotion and cocaine-seeking behavior, measured as a decrease in the ability of a cocaine priming injection to reinstate extinguished cocaine-conditioned place preference (CPP). Subsequent experiments showed that CP94253 given prior to conditioning sessions had no effect on acquisition of methamphetamine-CPP, a measure of drug reward; however, CP94253 given prior to testing attenuated expression of methamphetamine-CPP, a measure of drug seeking. To examine brain regions and cell types involved in CP94253 attenuation of methamphetamine-seeking, I examined changes in the immediate early gene product, Fos, which is a marker of brain activity involving gene transcription changes. Mice expressing methamphetamine-CPP showed elevated Fos expression in the VTA and basolateral amygdala (BlA), and reduced Fos in the central nucleus of the amygdala (CeA). In mice showing CP94253-induced attenuation of methamphetamine-CPP expression, Fos was increased in the VTA, NAc shell and core, and the dorsal medial caudate-putamen. CP94253 also reversed the methamphetamine-conditioned decrease in Fos expression in the CeA and the increase in the BlA. In drug-naïve, non-conditioned control mice, CP94253 only increased Fos in the CeA, suggesting that the increases observed in methamphetamine-conditioned mice were due to conditioning rather than an unconditioned effect of CP94253 on Fos expression. In conclusion, 5-HT1BR stimulation attenuates both cocaine and methamphetamine seeking in mice, and that the latter effect may involve normalizing activity in the amygdala and increasing activity in the mesolimbic pathway. These findings further support the potential efficacy of 5-HT1BR agonists as pharmacological interventions for psychostimulant craving in humans.
ContributorsDer-Ghazarian, Taleen (Author) / Neisewander, Janet (Thesis advisor) / Olive, Foster (Committee member) / Newbern, Jason (Committee member) / Wu, Jie (Committee member) / Arizona State University (Publisher)
Created2018