Barrett, The Honors College Thesis/Creative Project Collection
Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.
Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.
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Description
Polysubstance abuse is far more common than single substance abuse. One of the most widely abused, yet greatly understudied combination of drugs is the simultaneous use of methamphetamine (meth) and alcohol. Because little research has been conducted on the co-abuse of meth and alcohol, it is important to study the behavioral and neural mechanisms underlying the use of both to combat addiction and come closer to finding an effective treatment of this form of drug abuse. This study uses a rodent model to attempt to identify the mechanisms underlying this co-abuse through the stimulation of the medial forebrain bundle (MFB) and thus the activation of the mesocorticolimbic pathway, the brain's pleasure circuit. First, self-stimulation thresholds (the lowest electrical current the rats are willing to respond for) were determined using a process called Discrete Trials Training. This threshold was later used as a baseline measure to reference when the rats were administered the drugs of abuse: meth and alcohol, both alone and in combination. Our overall results did not show any significant effects of combining alcohol and meth relative to the effects of either drug alone, although subject attrition may have resulted in sample sizes that were statistically underpowered. The results of this and future studies will help provide a clearer understanding of the neural mechanisms underlying the polyabuse of meth and alcohol and can potentially lead to more successfully combating and treating this addiction.
ContributorsDrafton, Kaitlyn Marie (Author) / Olive, Foster (Thesis director) / Glenberg, Arthur (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Chronic restraint stress leads to apical dendritic retraction in CA3 pyramidal neurons and often no quantifiable changes in CA1 dendritic complexity. When chronic stress ends, a post-stress recovery period results in an enhancement in CA3 dendritic complexity. We investigated the relationship between CA3 and CA1 pyramidal neurons to determine whether dendritic restructuring in CA3 neurons leads to region-specific changes in the dendritic complexity of CA1 neurons. Adult male Sprague-Dawley rats were restrained (wire mesh, 6h/d/21d) and brains were removed soon after restraint ended (Str-Imm) or after a 21d post-stress recovery period (Str-Rec). In addition, BDNF downregulation targeting the CA3 region prevents enhancement in dendritic complexity following recovery in chronically stressed rats, providing robust conditions to investigate the CA3-CA1 relationship. Consequently, rats were infused into the CA3 area with either an AAV vector with a coding sequence against BDNF (shRNA) or a sequence with no known mRNA complements (Scr). Apical and basal dendritic complexity of CA3 and CA1 was quantified by counting total dendritic bifurcations and dendritic intersections using the Sholl analysis (20 µm distances from soma). Please note that the quantification of the CA3 dendritic arbors was not part of this thesis project. The outcome of that investigation revealed that apical CA3 dendritic retraction was found in Str-Imm-Scr and Str-Rec-shRNA. For the CA1 apical area, gross dendritic bifurcation differences were not detected, but the Sholl quantification revealed regionally-enhanced dendritic complexity that varied by distance from the soma at the distal apical dendrites (Str-Imm-Scr) and proximal basal dendrites (Str-Rec-shRNA). For the latter, significant increases in basal branch points were detected with total branch point quantification method. Moreover, a correlation using all groups revealed a significant inverse relationship between CA3 apical dendritic complexity and CA1 basal dendritic complexity. The results demonstrate that chronic stress-induced CA3 apical dendritic retraction may relate to region-specific changes in CA1 dendritic complexity. The inability of past studies to detect changes in CA1 dendritic complexity may be due to the shortcoming of gross dendritic arbor measures in accounting for subtle region-specific alterations. To address this, the current study included a cohort with BDNF downregulated in the CA3 region. Overall, this suggests that decreased levels of BDNF in the hippocampus provide robust conditions in which changes to CA1 dendritic complexity can be detected.
ContributorsDaas, Eshaan Jatin (Author) / Conrad, Cheryl (Thesis director) / Orchinik, Miles (Committee member) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12