Methamphetamine-induced hyperactivity and reinforcement learning in rats selectively bred for high and low voluntary running

2015 ◽  
Author(s):  
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Andrew S. Sage

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The goal of the present research was to assess two lines of Wistar rats selectively bred for high (HVR) and low (LVR) voluntary wheel running, in comparison to a line of control (WT) rats. As previous research has outlined the benefits of voluntary exercise on substance abuse, this study investigated the role of possible genetic differences between rat lines on sensitivity to methamphetamine (Experiment 1), motivation to work for and self-administer methamphetamine (Experiment 2a), and learning to press a lever for a food reward (Experiment 2b). Experiment 1 investigated sensitivity to methamphetamine in HVR, LVR, and WT rats by comparing locomotor behavior after methamphetamine administration. Experiment 1 found that both HVR and LVR rats were less sensitive to the locomotor activating properties of methamphetamine compared to WT rats. Experiment 2a and 2b investigated learning to press a lever for a food pellet or an infusion of methamphetamine in HVR, LVR, and WT rats. Experiment 2a found that both HVR and LVR rats were less sensitive to the reinforcing properties of methamphetamine compared to WT rats, evidenced by their reduced lever pressing behavior. Experiment 2b found that HVR rats pressed a lever less for a food pellet compared to both LVR and WT rats, suggesting that HVR rats alone may value a food pellet as a behavioral reinforcer less than the other two rat lines. The results of this preliminary investigation suggest that exercise may be both necessary and sufficient to produce effects on drug use behaviors. One's (genetic) predisposition to engage in exercise may be independent of one's ability to benefit from exercise.

2014 ◽  
Author(s):  
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Jacob Daniel Brown

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The Booth lab at the University of Missouri has selectively-bred Wistar rats for low (LVR) and high (HVR) voluntary running behavior as a model for examining the genetic and physiological origins of physical activity motivation. The major advantage of selective breeding over non-natural methods of genetic engineering is the perpetuation of naturally-existing, polygenic milieus that dictate complex behaviors or phenotypes (e.g. motivation to be physically active, etiology of obesity). Since most genes and physiological systems are pleiotropic and function as modular networks, a "by-product" of selective breeding is the co-selection of traits sharing some common genetic origins with the selected trait. Overall, the major emphasis of my dissertation was two-fold: (1) the elucidation of behavioral traits co-selected with low and high physical activity motivational behavior and (2) the effect of voluntary running in a mildly stressful environment on the dentate gyrus transcriptome of rats selectively bred for low voluntary running. Emphasis 1 (Chapters 2 and 3) was approached by measuring the performance of LVR and HVR rats in behavioral tests classically designed to measure non-wheel running locomotor activity behavior (i.e. open field test), sensitivity to drugs of abuse (i.e. cocaine-induced locomotor activity), anxiety-like behavior (i.e. elevated plus maze), depressive-like behavior (i.e. forced swim test), and nociception (i.e. thermal and mechanical stimulus). Emphasis 2 was approached by using RNA sequencing (RNA-seq) to map the transcriptome of the dentate gyrus after exposing sedentary and wheel running LVR and WT rats to 5 weeks of chronic mild stress (CMS). The results from Chapters 2 and 3 demonstrate that LVR and HVR rats have co-selected other behaviors, which suggest that they may be a valuable model for an array of research disciplines including: (1) the investigation of the genetic basis for physical activity motivation, (2) hyperactivity, (3) sensitivity to drugs of abuse (e.g. addiction), (4) emotional/stress disorders (e.g. anxiety and depression), and (5) nociception as well as the interactions between these complex phenotypes. The results from Chapter 4 provide transcriptomic evidence that low amounts of voluntary running performed by female LVR rats in a CMS environment are sufficient for eliciting robust changes in dentate gyrus transcriptome that included gene expression signatures associated with elevated synaptic plasticity, improved memory function, and increased blood vessel development.


2015 ◽  
Author(s):  
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Erik Ladomersky

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Copper is an essential nutrient. It plays an important role in development, pigmentation, neurological function, and immune defense. Copper deficiency is known to make host's more susceptible to infection. In this work we show that two copper proteins, ATP7A and ceruloplasmin, are important for host defense against bacterial infection. Studies have shown ATP7A is responsible for increasing copper concentrations inside the phagosome. Our study sheds light on the role of Atp7a and copper in adaptive immunity, and provide a biochemical model for understanding the relationship between copper malnutrition and susceptibility to infection. Iron, another essential nutrient, is linked with copper through the actions of copper-dependent proteins which play a role in maintaining normal iron levels in the blood. One of these proteins is ceruloplasmin, a protein that is also upregulated during infection. Our study sheds light onto why this protein is necessary for host defense against Salmonella infection.


2017 ◽  
Author(s):  
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Timothy R. Moake

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The challenge-hindrance stressor framework suggests that most workers experience challenge stressors positively and hindrance stressors negatively. However, research has shown that both types of stressors are positively related to psychological strain, a negative outcome. Using the transactional theory of stress, I examined whether and how individuals' appraisals of challenge and hindrance stressors and their goal orientations influence the positive relationships between both types of stressors and psychological strain. I surveyed 278 full-time employees from various occupations twice over a two-week span. My findings revealed that despite challenge stressors' positive conceptualization, individuals appraise them negatively as constraints. Additionally, I found that constraint appraisals are one mechanism that influences the positive relationship between challenge stressors and psychological strain. Lastly, my results also indicated that individuals with a stronger learning goal orientation are more likely to appraise both types of stressors as opportunities and individuals with a stronger performance-avoid goal orientation are more likely to appraise both types of stressors as constraints.


2017 ◽  
Author(s):  
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Krisztina A. Pusok

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] While the role of firms has been acknowledged in existent research in political economy, it has played a rather peripheral role in the study of environmental politics, specifically in understanding environmental governance. In this dissertation, I seek to identify what the role of the private sector is in pushing the global environmental agenda. Specifically, I seek to offer alternative explanations for why firms choose to form these regimes, by drawing on existent comparative and international relations literatures focusing on political economy, governance, and the role of non-state actors. Additionally, I discuss the conditions determining firms to form private environmental regimes, as well as the economic and political consequences of this growing dynamic. Lastly, I investigate the mechanisms tying together different actors in terms of their environmental governance interactions.


2019 ◽  
Author(s):  
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Emilee J. Howland-Davis

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] My dissertation argues that medieval and early modern English romances provided magic a safe space where authors and audiences engaged with the ideas of magic and superstition free from the risk of condemnation and the inquisition of medieval and early modern secular and religious authorities. The term safe space is a contemporary idea used to discuss spaces, both literal and figurative, where people who identify as LGTBQ+ are welcomed and free to express themselves. While the modern idea of a safe space has a very specific group of users and uses, it is the figurative idea of a safe space which I argue can be applied to otherworlds in medieval and early modern romances. I discuss late medieval and early modern romances as well as their interaction with and difference from historical records, trials, and treatises on magic. My methodology combines a historicist approach with Marxist and feminist theory in its exploration of magical safe spaces. The later Middle Ages were a time of increased scrutiny of non-religious behaviors, a narrowing of what constituted witchcraft and diabolism, and an upsurge in the numbers of heretical accusations and trials. Similarly, early modern England experienced an increase in accusations and investigations of magic, witchcraft, and heresy. My dissertation draws connections between historical documents and medieval and early modern literature and argues that as societal concerns about feminine heretical practice increased, literature found safe ways to explore these ideas. In doing this, medieval and early modern romance became a safe space for the exploration of magic generally and female magic users specifically.


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Stephen W Luckey ◽  
Nathan McLaughlin ◽  
Sherilynn Soo

Exercise training protects the heart against the adverse effects of cardiovascular disease. Recent studies have identified a number of cardiac adaptations including the activation of hypertrophic signaling pathways unique to exercise. However, the underlying mechanisms by which exercise confers cardioprotection are not entirely understood. This study aims to fill this gap by examining the role of voluntary exercise in the context of chronic β-adrenergic receptor stimulation. To do this, we developed a novel experimental model in which nine-week-old female and male CB6F1 hybrid mice were subjected to 5 weeks of voluntary wheel running (EX) or housed under sedentary conditions (SED). For the final two weeks, mice were administered either vehicle (VEH) or isoproterenol (ISO, 30mg/kg/day) via an osmotic pump. As expected, we found that ISO significantly increased heart size in sedentary females and males (SED+ISO) compared to sedentary mice receiving VEH (SED+VEH). Consistent with previously published data, exercise capacity was also greater in females compared to males with regards to running duration and distance regardless of the experimental group. While exercise capacity was not affected by the administration of VEH, mice receiving ISO (EX+ISO) exercised significantly less. Cardiac growth in EX+VEH mice was significantly increased in both females and males compared to their respective SED+VEH counterparts. Importantly, EX+ISO females and males have significantly larger hearts than their respective SED+ISO cohorts. Moreover, EX+ISO mice also exhibited greater increases in cardiac size as compared to their respective EX+VEH counterparts. Thus, we conclude that there appears to be an additive effect of voluntary exercise and ISO administration in both females and males in terms of cardiac growth. These preliminary data are in contrast to previously published data which found that controlled exercise programs reduced cardiac hypertrophy under conditions of chronic β-adrenergic receptor stimulation. We are currently investigating the processes that lead to the larger heart sizes in the EX+ISO mice and aim to better understand the underlying mechanisms of exercise-mediated cardioprotection.


Author(s):  
Jane Yeahin Pyo ◽  
Nikki Usher

This chapter is a reminder that practice and theory have gone hand in hand since the beginning of professional journalism. However, this history and this partnership have been lost somewhat, particularly when it comes to PhD research. By calling back to the land-grant mission at the universities home to the first schools of journalism in the United States (the University of Missouri, the University of Illinois, the University of Wisconsin), the chapter recalls how the focus on skills and on understanding mass communication was aligned with the mission of journalism education. The chapter examines the founding of the Institute of Communications Research at the University of Illinois and its PhD program that focused on applied journalism and mass communication research, explaining the role of legendary journalism scholar James Carey in recentering (and decentering) the tension between practice and research.


2018 ◽  
Author(s):  
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Ashutosh Shripad Phadte

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Cataractogenesis in the eye lens occurs as a result of protein aggregation. Of the multiple mutations in [alpha]A-crystallins associated with the development of congenital hereditary cataract, three identified mutations target R21 within the N- terminal domain of the protein. On structural and functional characterization of a recently identified mutant of [alpha]A-crystallin, [alpha]A-R21Q, we revealed the contribution of R21 in dictating the interaction of [alpha]A-crystallin with other proteins. [alpha]A-R21Q showed and enhanced chaperone-like function, and increased binding to lens fiber cell membranes. Transduction of mutant proteins in ARPE-19 cells prevented their apoptosis in the presence of oxidative stress, suggesting a role for R21 in modulating the anti-apoptotic function of [alpha]A-crystallin. In addition, the R21Q point mutation rescued the chaperone-like activity of [alpha]A-G98R crystallin as well as palliated [alpha]A-G98R mediated cytotoxicity otherwise observed in transduction experiments. Although another mutation, R157Q rescued the chaperone-like activity of [alpha]A-G98R, the double mutant exhibited a loss of its cytoprotective function. The results therefore implicate an important role of R21 in regulating the functional aspect of [alpha]A-crystallin. [alpha]A-crystallin derived peptides have been shown to prevent non-specific aggregation of unfolding proteins in vitro. We show that the [alpha]A-crystallin derived mini-chaperone (mini-[alpha]A) mediated stabilization of self-aggregating [alpha]A-G98R crystallin and bovine [subscript]-crystallin occurs via compensation of lost surface charge. The observation therefore suggests a plausible mechanism of action of [alpha]A-crystallin derived peptides of therapeutic interest.


2017 ◽  
Author(s):  
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Marina A. Hendricks

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Like their professional counterparts, high school journalists are confronting the societal and technological forces that are reshaping journalism. As members of journalism's next generation, high school journalists are charged with the responsibility of carrying journalism forward long after senior journalists exit the newsroom. This case study incorporated ethnographic observation and interviews to examine how high school journalists are socialized into journalism as an occupational ideology (Deuze, 2005). It focused on how high school journalists make meaning of public service, objectivity, autonomy, immediacy, and ethics through the intersection of their journalistic roles. It also looked at how high school journalists are socialized into journalism in the educational setting. Lastly, it considered the role of agents of socialization, such as individual educators, peers, family, part-time work, and the media. The findings suggest that high school journalists who practice free of threats from prior review and restraint are acclimating to the shared autonomy of the multimedia environment. High school journalists also are adapting to new considerations of immediacy that provide them with flexibility to act as disseminators or interpreters, as the situation warrants. Finally, high school journalists in an autonomous environment exert a strong socialization influence on their peers.


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