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Description
MicroRNAs are small, non-coding transcripts that post-transcriptionally regulate expression of multiple genes. Recently microRNAs have been linked to the etiology of neuropsychiatric disorders, including drug addiction. Following genome-wide sequence analyses, microRNA-495 (miR-495) was found to target several genes within the Knowledgebase of Addiction-Related Genes (KARG) database and to be highly expressed in the nucleus accumbens (NAc), a pivotal brain region involved in reward and motivation. The central hypothesis of this dissertation is that NAc miR-495 regulates drug abuse-related behavior by targeting several addiction-related genes (ARGs). I tested this hypothesis in two ways: 1) by examining the effects of viral-mediated miR-495 overexpression or inhibition in the NAc of rats on cocaine abuse-related behaviors and gene expression, and 2) by examining changes in NAc miR-495 and ARG expression as a result of brief (i.e., 1 day) or prolonged (i.e., 22 days) cocaine self-administration. I found that behavioral measures known to be sensitive to motivation for cocaine were attenuated by NAc miR-495 overexpression, including resistance to extinction of cocaine conditioned place preference (CPP), cocaine self-administration on a high effort progressive ratio schedule of reinforcement, and cocaine-seeking behavior during both extinction and cocaine-primed reinstatement. These effects appeared specific to cocaine, as there was no effect of NAc miR-495 overexpression on a progressive ratio schedule of food reinforcement. In contrast, behavioral measures known to be sensitive to cocaine reward were not altered, including expression of cocaine CPP and cocaine self-administration under a low effort FR5 schedule of reinforcement. Importantly, the effects were accompanied by decreases in NAc ARG expression, consistent with my hypothesis. In further support, I found that NAc miR-495 levels were reduced and ARG levels were increased in rats following prolonged, but not brief, cocaine self-administration experience. Surprisingly, inhibition of NAc miR-495 expression also decreased both cocaine-seeking behavior during extinction and NAc ARG expression, which may reflect compensatory changes or unexplained complexities in miR-495 regulatory effects. Collectively, the findings suggest that NAc miR-495 regulates ARG expression involved in motivation for cocaine. Therefore, using microRNAs as tools to target several ARGs simultaneously may be useful for future development of addiction therapeutics.
ContributorsBastle, Ryan (Author) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Nikulina, Ella (Committee member) / Perrone-Bizzozero, Nora (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2016
Description
ADHD is a childhood neurobehavioral disorder characterized by inordinate levels of hyperactivity, inattention and impulsivity. The inability to withhold a reinforced response, or response inhibition capacity (RIC), is one aspect of impulsivity associated with ADHD. The first goal of this dissertation was to evaluate the fixed minimum interval (FMI) schedule as a method for assessing RIC. Chapter 2 showed that latencies were substantially more sensitive than FMI-derived estimates of RIC to the effects of pre-feeding and changes in rate and magnitude of reinforcement. Chapter 3 examined the ability of the FMI to discriminate between spontaneously hypertensive rats (SHR), an animal model of ADHD, and Wistar Kyoto (WKY) controls. Results from Chapter 3 showed that RIC was not substantially different between SHR and WKY rats. However, latencies were significantly shorter for SHRs than for WKYs suggesting incentive motivation differed between strains. The second goal of this dissertation was to examine the sensitivity of the SHR to nicotine. ADHD is a risk factor for tobacco dependence. The goal of Chapters 4 and 5 was to determine whether the SHR provided a model of ADHD-related tobacco sensitivity. Chapter 4 examined nicotine's locomotor and rewarding effects in adolescent SHRs using the conditioned place preference (CPP) procedure. SHRs developed CPP to the highest nicotine dose tested and were sensitive to nicotine's locomotor-enhancing properties. WKY controls did not develop CPP to any nicotine dose tested and were not sensitive to nicotine's locomotor properties. However, it is likely that nicotine effects were obscured by a pseudo-conditioning to saline in WKYs. Chapter 5 demonstrated that SHRs were more active than WKYs in the open-field but not in the Rotorat apparatus. Results also showed that SHRs and WKYs were both sensitive to nicotine's locomotor sensitizing effects. However, WKYs were more sensitive than SHRs to nicotine's locomotor suppressing effects. Collectively, results from Chapters 4 and 5 show that SHRs are sensitive to the rewarding and locomotor-enhancing properties of nicotine. However, more research is necessary to confirm that SHRs are a suitable model for studying ADHD-related tobacco use.
ContributorsWatterson, Elizabeth (Author) / Sanabria, Federico (Thesis advisor) / Olive, Foster (Thesis advisor) / Chassin, Laurie (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2015
Description
Globally, addiction to stimulants such as methamphetamine (METH) remains a significant public health problem. Despite decades of research, no approved anti-relapse medications for METH or any illicit stimulant exist, and current treatment approaches suffer from high relapse rates. Recently, synthetic cathinones have also emerged as popular abused stimulants, leading to numerous incidences of toxicity and death. However, contrary to traditional illicit stimulants, very little is known about their addiction potential. Given the high relapse rates and lack of approved medications for METH addiction, chapters 2 and 3 of this dissertation assessed three different glutamate receptor ligands as potential anti-relapse medications following METH intravenous self-administration (IVSA) in rats. In chapters 4 through 7, using both IVSA and intracranial self-stimulation (ICSS) procedures, experiments assessed abuse liability of the popular synthetic cathinones 3,4-Methylenedioxypyrovalerone (MDPV) , methylone, α-pyrrolidinovalerophenone (α-PVP) and 4-methylethylcathinone (4-MEC). Results from these seminal studies suggest that these drugs possess similar abuse potential to traditional illicit stimulants such as METH, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA). Finally, studies outlined in chapter 8 assessed the potential neurotoxic or adverse cognitive effects of METH and MDPV following IVSA procedures for the purpose of identifying potential novel pharmacotherapeutic targets. However, results of these final studies did not reveal neurotoxic or adverse cognitive effects when using similar IVSA procedural parameters that were sufficient for establishing addiction potential, suggesting that these parameters do not allow for sufficient drug intake to produce similar neurotoxicity or cognitive deficits reported in humans. Thus, these models may be inadequate for fully modeling the adverse neural and psychological consequences of stimulant addiction. Together, these studies support the notion for continued research into the abuse liability and toxicity of METH and synthetic cathinones and suggest that refinements to traditional IVSA models are needed for both more effective assessment of potential cognitive and neural deficits induced by these drugs and screening of potentially clinically efficacious pharmacotherapeutics.
ContributorsWatterson, Lucas (Author) / Olive, Michael F (Thesis advisor) / Czyzyk, Traci (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2014
Description
Religion and the belief in supernatural agents have been assumed to play an important role in encouraging prosocial behavior. However, different studies conducted have shown a complex relation between religion and prosociality. For example, Darley & Batson (1973) found that religious people do not always help strangers. In the present study, Christian participants were primed with benevolent commandments attributed to either the Bible or past historical figures or secular, non-benevolent quotes (control). I then measured their willingness to help pick up envelopes dropped by either a Muslim (wearing a hijab) or non-Muslim confederate woman. The results show that subjects primed with Bible or presidential quotes about benevolence were more likely to be helpful to the Muslim confederate than those in the control group. Differences between the Bible and presidential condition were not significant. I conclude that an authority, whether it be a president or God, promoting benevolence can increase prosocial behaviors toward out-group members.
ContributorsMemon, Rabia (Author) / Cohen, Adam (Thesis director) / Knight, George (Committee member) / Okun, Morris (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
The front cover of Uncle What-Is-It is Coming to Visit, a 1993 children’s book by Michael-Willhoite, features two white children frightened by the hairy arm and upturned wrist of an unseen adult. The arm is clad in a frilly pink and orange sleeve, and gaudy bracelets hang from the wrist. The plot hinges on the children’s uncertainty about an uncle they have yet to meet; they know he is gay but are unsure of what it means. Before their mother can explain, she is distracted by a kitchen mishap and the siblings turn to other neighborhood children for answers. They encounter a host of descriptions that terrify them: one neighbor describes gay people as “fags [and] queers [who] really want to be women.” He shows the children a newspaper clipping photo of “a large man dressed in a frilly dress [with] a turban piled high with fruit on his head,” an implicitly racialized caricature reminiscent of Latina style icon Carmen Miranda. Another neighbor describes gay people as “dressed up in black leather. Zippers and chains all over...Dark glasses [and] chaps” (Willhoite, 1993). After having nightmares of men with sinister expressions in tropical-themed drag and leather, the children are overjoyed to discover that their uncle seems “normal.” Relative to depictions of other gay people in the book, Uncle Brett is normal because he is nonthreatening—he is white with short, straight, brown hair; he wears a plain, blue, collared shirt and brown dress pants; he carries a brown briefcase; and he enjoys and excels at activities appropriate for his gender, like catch. Although the book seems to have an affirming message about accepting queer people, it sends a clear message about which queer people are to be feared by children and which are nonthreatening. Nonthreatening queers are those who seem most like people mainstream western society considers normal: people who conform to expected gender roles, who have a vested interest parenting, and who are white and middle-upper class. These nonthreatening queers are by far the most represented in queer-themed literature for children. Based on a survey of 68 children’s books with queer characters, this paper argues that the representation of queer identities in children’s literature upholds more than challenges heteronormativity. I will first address ways many of the books perpetuate gender normativity by problematizing young male characters’ gender-transgressing behavior, portraying queer adults with less threatening gender presentations, and upholding gender binarism; next, I will address how the majority of the books promote repro-narrativity by focusing on monogamous couples’ strong desires and concerted efforts to have/raise children; I will then address race and class and the way white and upper-middle class queer characters are overrepresented while non-white and lower-class queer characters are underrepresented or not represented at all.
ContributorsLester, Jasmine (Author) / Danielson, Marivel (Thesis director) / Blasingame, James (Committee member) / Kuo, Karen (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Visual aides, such as PowerPoint slides, hand-outs, and lecture notes on whiteboards, are often used in classrooms to convey important content to learners, especially in high school and college. When using these visual learning aides, it is important to consider which qualities of these presentations can affect learning— positively or negatively—and how those qualities interact with individual student characteristics. In the present study, we examine the overlap between audio and text and how the effects of overlap potentially interact with reading comprehension abilities. The examination of these potential influences on learning in this study is inspired by Cognitive Load Theory, the Dual-Channel Assumption, and prior research.
ContributorsHarry, Danielle (Author) / McNamara, Danielle (Thesis director) / Presson, Clark (Committee member) / Jackson, Tanner (Committee member) / Roscoe, Rod (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
The lonely, empty face panhandling on the street corner has a story to tell. At first glance, most people write the homeless off as less than worthy. However, there is a deeper connection and understanding of relationships and a sense of community unseen by the majority of passer-byers. Amidst the humdrum beat of every day life, there is toil to find basic necessities such as food, water, sanitation, and a place to rest. At the same time, there is laughter and friendship as they help one another through the hostilities of their circumstances. Combining the creative elements of photojournalism and qualitative interviewing, the basic daily needs and struggles of the homeless will be delved into to answer how friendship is pertinent to survival on the streets.
ContributorsFisher, Meghan (Author) / Hruschka, Daniel (Thesis director) / Hita, Liza (Committee member) / Newland, Judy (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Prospective memory is defined as remembering to carry out specified actions in the future. Research has suggested that prospective memory retrieval is reliant on multiple cognitive processes to function, and the ways in which these different processes are used is dependent on a variety of variables relating to the prospective memory task at hand. The current study focuses on the strength of the association between the prospective
memory cue and the prospective memory intention. Based on literature suggesting that aspects of prospective memory are reliant on executive control functioning, the current study examined the possibility that executive control depletion would affect prospective memory ability on subsequent tasks. Results showed that depletion of executive control resources, measured objectively, did not impair prospective memory in either a low or
high cue-association condition. However, participants‟ subjective assessment of their own fatigue correlated significantly with their subsequent prospective memory performance, regardless of association condition. The results of the study indicate that depletion studies that fail to account for both objective and subjective measures suffer from an unclear interpretation of effects, and that recognition of perceived expectancies
of cognitive resource limitation can assist in improving prospective memory ability.
memory cue and the prospective memory intention. Based on literature suggesting that aspects of prospective memory are reliant on executive control functioning, the current study examined the possibility that executive control depletion would affect prospective memory ability on subsequent tasks. Results showed that depletion of executive control resources, measured objectively, did not impair prospective memory in either a low or
high cue-association condition. However, participants‟ subjective assessment of their own fatigue correlated significantly with their subsequent prospective memory performance, regardless of association condition. The results of the study indicate that depletion studies that fail to account for both objective and subjective measures suffer from an unclear interpretation of effects, and that recognition of perceived expectancies
of cognitive resource limitation can assist in improving prospective memory ability.
ContributorsCook, Carson (Author) / Brewer, Gene (Thesis director) / Presson, Clark (Committee member) / Homa, Donald (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Social proof and mismatch of self-preference have been assumed to play an important role in the inference of value. They can be influential factors when it comes to decision-making in a mate-selection environment. In this thesis study, participants took an online survey in the form of a dating website. They answered a series of questions about the traits they would like to see in a potential mate. They were then presented with four potential mates and asked to rank them by their preferences. The results show that participants most preferred the potential mate with a high social proof and a low mismatch of self-preference and least preferred the potential mate with a low social proof and a high mismatch of self-preference. When comparing just social proof and mismatch of self-preference, there was not an interaction effect between the two. I conclude that even though social proof is a powerful influencing factor by itself, it did not have the power to trump the mismatch of self-preference.
ContributorsAkhter, Sumbal (Author) / Kwan, Virginia (Thesis director) / Knight, George (Committee member) / Cohen, Adam (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12