Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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- All Subjects: Behavioral Sciences
- Genre: Doctoral Dissertation
Description
5-HT2A receptor (R) antagonists and 5-HT2CR agonists attenuate reinstatement of cocaine-seeking behavior (i.e., incentive motivation). 5-HT2Rs are distributed throughout the brain, primarily in regions involved in reward circuitry, including the prefrontal cortex (PFC), caudate putamen (CPu), and basolateral (BlA) and central (CeA) amygdala. Using animal models, we tested our hypotheses that 5-HT2ARs in the medial (m) PFC mediate the incentive motivational effects of cocaine and cocaine-paired cues; 5-HT2ARs and 5-HT2CRs interact to attenuate cocaine hyperlocomotion and functional neuronal activation (i.e, Fos protein); and 5-HT2CRs in the BlA mediate the incentive motivational effects of cocaine-paired cues and anxiety-like behavior, while 5-HT2CRs in the CeA mediate the incentive motivational effects of cocaine. In chapter 2, we infused M100907, a selective 5-HT2AR antagonist, directly into the mPFC and examined its effects on reinstatement of cocaine-seeking behavior. We found that M100907 in the mPFC dose- dependently attenuated cue-primed reinstatement, without affecting cocaine-primed reinstatement, cue-primed reinstatement of sucrose-seeking behavior, or locomotor activity. In chapter 3, we used subthreshold doses of M100907 and MK212, a 5-HT2CR agonist, to investigate whether these compounds interact to attenuate cocaine hyperlocomotion and Fos protein expression. Only the drug combination attenuated cocaine hyperlocomotion and cocaine-induced Fos expression in the CPu, but had no effect on spontaneous locomotion. Finally, in chapter 4 we investigated the effects of a 5- HT2CR agonist in the BlA and CeA on cocaine-seeking behavior and anxiety-like behavior. We found that CP809101, a selective 5-HT2CR agonist, infused into the BlA increased anxiety-like behavior on the elevated plus maze (EPM), but failed to alter cocaine-seeking behavior. CP809101 infused into the CeA attenuated cocaine-primed reinstatement and this effect was blocked by co-administration of a 5-HT2CR antagonist. Together, these results suggest that 5-HT2ARs in the mPFC are involved in cue-primed reinstatement, 5-HT2A and 5-HT2CRs may interact in the nigrostriatal pathway to attenuate cocaine hyperlocomotion and Fos expression, and 5-HT2CRs are involved in anxiety-like behavior in the BlA and cocaine-primed reinstatement in the CeA. Our findings add to the literature on the localization of 5-HT2AR antagonist and 5-HT2CR agonist effects, and suggest a potential treatment mechanism via concurrent 5-HT2AR antagonism and 5-HT2CR agonism.
ContributorsPockros, Lara Ann (Author) / Neisewander, Janet L (Thesis advisor) / Olive, Michael F (Committee member) / Conrad, Cheryl D. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
Description
Two groups of cochlear implant (CI) listeners were tested for sound source localization and for speech recognition in complex listening environments. One group (n=11) wore bilateral CIs and, potentially, had access to interaural level difference (ILD) cues, but not interaural timing difference (ITD) cues. The second group (n=12) wore a single CI and had low-frequency, acoustic hearing in both the ear contralateral to the CI and in the implanted ear. These `hearing preservation' listeners, potentially, had access to ITD cues but not to ILD cues. At issue in this dissertation was the value of the two types of information about sound sources, ITDs and ILDs, for localization and for speech perception when speech and noise sources were separated in space. For Experiment 1, normal hearing (NH) listeners and the two groups of CI listeners were tested for sound source localization using a 13 loudspeaker array. For the NH listeners, the mean RMS error for localization was 7 degrees, for the bilateral CI listeners, 20 degrees, and for the hearing preservation listeners, 23 degrees. The scores for the two CI groups did not differ significantly. Thus, both CI groups showed equivalent, but poorer than normal, localization. This outcome using the filtered noise bands for the normal hearing listeners, suggests ILD and ITD cues can support equivalent levels of localization. For Experiment 2, the two groups of CI listeners were tested for speech recognition in noise when the noise sources and targets were spatially separated in a simulated `restaurant' environment and in two versions of a `cocktail party' environment. At issue was whether either CI group would show benefits from binaural hearing, i.e., better performance when the noise and targets were separated in space. Neither of the CI groups showed spatial release from masking. However, both groups showed a significant binaural advantage (a combination of squelch and summation), which also maintained separation of the target and noise, indicating the presence of some binaural processing or `unmasking' of speech in noise. Finally, localization ability in Experiment 1 was not correlated with binaural advantage in Experiment 2.
ContributorsLoiselle, Louise (Author) / Dorman, Michael F. (Thesis advisor) / Yost, William A. (Thesis advisor) / Azuma, Tamiko (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2013
Description
There are several visual dimensions of food that can affect food intake, example portion size, color, and variety. This dissertation elucidates the effect of number of pieces of food on preference and amount of food consumed in humans and motivation for food in animals. Chapter 2 Experiment 1 showed that rats preferred and also ran faster for multiple pieces (30, 10 mg pellets) than an equicaloric, single piece of food (300 mg) showing that multiple pieces of food are more rewarding than a single piece. Chapter 2 Experiment 2 showed that rats preferred a 30-pellet food portion clustered together rather than scattered. Preference and motivation for clustered food pieces may be interpreted based on the optimal foraging theory that animals prefer foods that can maximize energy gain and minimize the risk of predation. Chapter 3 Experiment 1 showed that college students preferred and ate less of a multiple-piece than a single-piece portion and also ate less in a test meal following the multiple-piece than single-piece portion. Chapter 3 Experiment 2 replicated the results in Experiment 1 and used a bagel instead of chicken. Chapter 4 showed that college students given a five-piece chicken portion scattered on a plate ate less in a meal and in a subsequent test meal than those given the same portion clustered together. This is consistent with the hypothesis that multiple pieces of food may appear like more food because they take up a larger surface area than a single-piece portion. All together, these studies show that number and surface area occupied by food pieces are important visual cues determining food choice in animals and both food choice and intake in humans.
ContributorsBajaj, Devina (Author) / Phillips, Elizabeth D. (Thesis advisor) / Cohen, Adam (Committee member) / Johnston, Carol (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
Description
Patients with schizophrenia have deficits in sensorimotor gating, the ability to gate out irrelevant stimuli in order to attend to relevant stimuli. Prepulse inhibition (PPI) of the startle response is a reliable and valid model of sensorimotor gating across species. Repeated D2-like agonist treatment alleviates prior PPI deficits in rats, termed a PPI recovery, and is observable 28 days after treatment. The aim of the current project is to illuminate the underlying mechanism for this persistent change of behavior and determine the clinical relevance of repeated D2-like agonist treatment. Our results revealed a significant increase in Delta FosB, a transcription factor, in the nucleus accumbens (NAc) 10 days after repeated D2-like agonist treatment. Additionally, we investigated if Delta FosB was necessary for long-lasting PPI recovery and discovered a bilateral infusion of dominant-negative Delta JunD prevented PPI recovery after repeated D2-like agonist treatment. To further develop the underlying mechanism of PPI recovery, we observed that dominant negative mutant cyclic adenosine monophosphate (cAMP) response biding element protein (CREB) prevented repeated D2-like agonist-induced Delta FosB expression in the NAc. We then compared our previous behavioral and intracellular findings to the results of repeated aripiprazole, a novel D2-like partial agonist antipsychotic, to determine if repeated D2-like receptor agonist action is a clinically relevant pharmacological approach. As compared to previous PPI recovery and Delta FosB expression after repeated D2-like agonist treatment, we found similar PPI recovery and Delta FosB expression after repeated aripiprazole treatment in rats. We can conclude that repeated D2-like agonist treatment produces persistent PPI recovery through CREB phosphorylation and Delta FosB, which is necessary for PPI recovery. Furthermore, this pharmacological approach produces behavioral and intracellular changes similar to an effective novel antipsychotic. These findings suggest the underlying intracellular mechanism for sustained PPI recovery is clinically relevant and may be a potential target of therapeutic intervention to alleviate sensorimotor gating deficits, which are associated with cognitive symptoms of schizophrenia.
ContributorsMaple, Amanda (Author) / Hammer, Ronald P. (Thesis advisor) / Olive, Michael F (Committee member) / Gallitano, Amelia L (Committee member) / Conrad, Cheryl D. (Committee member) / Nikulina, Ella M (Committee member) / Arizona State University (Publisher)
Created2013
Description
The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (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
My dissertation contributes to a body of knowledge useful for understanding the evolution of subsistence economies based on agriculture from those based on hunting and gathering, as well as the development of formal rules and norms of territorial ownership in hunter-gatherer societies. My research specifically combines simple formal and conceptual models with the empirical analysis of large ethnographic and environmental data sets to study feedback processes in coupled forager-resource systems. I use the formal and conceptual models of forager-resource systems as tools that aid in the development of two alternative arguments that may explain the adoption of food production and formal territorial ownership among hunter-gatherers. I call these arguments the Uncertainty Reduction Hypothesis and the Social Opportunity Hypothesis. Based on the logic of these arguments, I develop expectations for patterns of food production and formal territorial ownership documented in the ethnographic record of hunter-gatherer societies and evaluate these expectations with large ethnographic and environmental data sets. My analysis suggests that the Uncertainty Reduction Hypothesis is more consistent with the data than the Social Opportunity Hypothesis. Overall, my approach combines the intellectual frameworks of evolutionary ecology and resilience thinking. The result is a theory of subsistence change that integrates elements of three classic models of economic development with deep intellectual roots in human ecology: The Malthusian, Boserupian and Weberian models. A final take home message of my study is that evolutionary ecology and resilience thinking are complementary frameworks for archaeologists who study the transition from hunting and gathering to farming.
ContributorsFreeman, Jacob (Author) / Anderies, John M (Thesis advisor) / Nelson, Margaret C. (Thesis advisor) / Barton, C Michael (Committee member) / Arizona State University (Publisher)
Created2014
Description
This research is particularly concerned with organizations’ advocacy of value-based change aimed at improving consumers’ well-being. This work contributes to the Transformative Services Research area and presents a conceptualization of the value-laden service organization (VLSO), which I define as organizations that advocate for specific value-based behaviors from consumers both within and beyond the particular service setting.
In a VLSO, consumers are expected to act in accordance with the values of the organization. If the consumer’s pre-existing value system is not aligned with the values of the service organization, the consumer may experience a sense of psychological disequilibrium, which can lead to unintended decrease in well-being. This research explores how value conflicts are managed by both the organization and by the consumers.
This work emerges out of an interpretive study of a Catholic-based homeless shelter for pregnant women. From it, I identify the practices of consumers and the service organization and explored their interactions. This has resulted in a theoretical conceptualization of a Rescue Institution, which combines aspects of both a Total Institution and a Reinventive Institution in a unique way. Further, I conceptualize a cycle of agency and authenticity that maps the dynamics of the consumer in a VLSO as they negotiate the structure/agency duality.
In gathering data, I used an interpretive approach over the course of three years’ of direct involvement with a service organization, St. Mary’s House. My methods included participant observation, collection of artifacts, and one-on-one in-depth interviews. I interviewed a total of 30 participants, whose transcribed interviews resulted in over 1500 pages of text. Analysis of themes and concepts occurred as a result of repeated examinations of both existing theory and data.
My findings reveal key organizational and consumer practices that negotiate the tension between structure and agency. Organizational practices include rules and social norms, as well as two forms of hierarchy. Consumer practices, often in response to organizational practices, include a cycle of agency and authenticity and participation in a shadow structure. These practices collectively influence consumer’s interpretive drift, which is their adoption of the organization’s values that creates internalized change. I conclude with implications for theory and service organization management. First, value priorities mean that tradeoffs must be made, which can cause unexpected and painful conflict. The experience of change, from both the consumer and service provider perspective, can be very messy. This process includes a dynamic and individual negotiation of authenticity and agency, which will be of interest in future studies. The service providers must be open to this process, carefully navigating their responses to the consumer’s dynamic authenticity, agency and values. Service providers should expect and acknowledge the conflict in consumers’ experience in order to foster their long-term perspective and perseverance.
In a VLSO, consumers are expected to act in accordance with the values of the organization. If the consumer’s pre-existing value system is not aligned with the values of the service organization, the consumer may experience a sense of psychological disequilibrium, which can lead to unintended decrease in well-being. This research explores how value conflicts are managed by both the organization and by the consumers.
This work emerges out of an interpretive study of a Catholic-based homeless shelter for pregnant women. From it, I identify the practices of consumers and the service organization and explored their interactions. This has resulted in a theoretical conceptualization of a Rescue Institution, which combines aspects of both a Total Institution and a Reinventive Institution in a unique way. Further, I conceptualize a cycle of agency and authenticity that maps the dynamics of the consumer in a VLSO as they negotiate the structure/agency duality.
In gathering data, I used an interpretive approach over the course of three years’ of direct involvement with a service organization, St. Mary’s House. My methods included participant observation, collection of artifacts, and one-on-one in-depth interviews. I interviewed a total of 30 participants, whose transcribed interviews resulted in over 1500 pages of text. Analysis of themes and concepts occurred as a result of repeated examinations of both existing theory and data.
My findings reveal key organizational and consumer practices that negotiate the tension between structure and agency. Organizational practices include rules and social norms, as well as two forms of hierarchy. Consumer practices, often in response to organizational practices, include a cycle of agency and authenticity and participation in a shadow structure. These practices collectively influence consumer’s interpretive drift, which is their adoption of the organization’s values that creates internalized change. I conclude with implications for theory and service organization management. First, value priorities mean that tradeoffs must be made, which can cause unexpected and painful conflict. The experience of change, from both the consumer and service provider perspective, can be very messy. This process includes a dynamic and individual negotiation of authenticity and agency, which will be of interest in future studies. The service providers must be open to this process, carefully navigating their responses to the consumer’s dynamic authenticity, agency and values. Service providers should expect and acknowledge the conflict in consumers’ experience in order to foster their long-term perspective and perseverance.
ContributorsRiker, Elise Briggs (Author) / Anderson, Laurel (Thesis advisor) / Ostrom, Amy (Committee member) / Dobscha, Susan (Committee member) / Arizona State University (Publisher)
Created2015
Description
Nationally, African Americans suffer disproportionately from diabetes; with 13.2% of African Americans diagnosed with diabetes compared to 7.6% of non-Hispanic whites (CDC, 2014). Nearly one-half of all people with diabetes are non-adherent to their oral medications; adherence to insulin therapy was 60%-80% (Brunton et al., 2011; Cramer, 2004; Rubin, 2005). This study explored the question, "What mechanisms are associated with adherence to diabetes medication, including insulin, for African Americans in the Southwest?" Twenty-three people participated in the study; 17 participated in interviews and six participated in gendered focus groups. A community-based participatory research (CBPR) approach engaged the African American community as partners in research.
Major themes emerging from the data included illness perception, support, and the process of medication adherence. Acceptance of the diabetes diagnosis was imperative for medication adherence. Stigmatization of diabetes was salient in the recruitment process and as it related to mechanisms for adherence. Furthermore, many informants were not aware of a family history of diabetes before their own diagnosis. Four gendered emerging typologies were identified, which further illuminated major themes. Moreover, an eight-step process of medication adherence model is discussed. The researcher was able to identify culturally compatible strategies that may be extended to those struggling with medication adherence. The implications section suggests a set of strategies that healthcare providers can present to people with diabetes in order to increase medication adherence.
Major themes emerging from the data included illness perception, support, and the process of medication adherence. Acceptance of the diabetes diagnosis was imperative for medication adherence. Stigmatization of diabetes was salient in the recruitment process and as it related to mechanisms for adherence. Furthermore, many informants were not aware of a family history of diabetes before their own diagnosis. Four gendered emerging typologies were identified, which further illuminated major themes. Moreover, an eight-step process of medication adherence model is discussed. The researcher was able to identify culturally compatible strategies that may be extended to those struggling with medication adherence. The implications section suggests a set of strategies that healthcare providers can present to people with diabetes in order to increase medication adherence.
ContributorsWardian, Jana (Author) / Marsiglia, Flavio F (Thesis advisor) / Sun, Fei (Committee member) / Shaibi, Gabriel (Committee member) / Arizona State University (Publisher)
Created2015