Matching Items (3)
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- All Subjects: Drug Abuse
- Creators: Burnam-Fink, Michael
- Creators: Johnston, Caitlin
- Creators: Malone, Shane
Description
Intermittent social defeat stress produces vulnerability to drugs of abuse, a phenomena known as cross-sensitization, which is proceeded by a corresponding upregulation of ventral tegmental area (VTA) mu-opioid receptors (MORs). Since VTA MORs are implicated in the expression of psychostimulant sensitization, they may also mediate social stress-induced vulnerability to drugs of abuse. Social stress and drugs of abuse increase mesolimbic brain-derived neurotrophic factor (BDNF) signaling with its receptor, tropomyosin-related kinase B (TrkB). These studies examined whether VTA MOR signaling is important for the behavioral and cellular consequences of social stress. First, the function of VTA MORs in the behavioral consequences of intermittent social defeat stress was investigated. Lentivirus-mediated knockdown of VTA MORs prevented social stress-induced cross-sensitization, as well as stress-induced social avoidance and weight gain deficits. Next it was examined whether VTA MOR expression is critical for stress-induced alterations in the mesocorticolimbic circuit. At the time cross-sensitization was known to occur, lentivirus-mediated knockdown of VTA MORs prevented stress-induced increases in VTA BDNF and its receptor, TrkB in the nucleus accumbens (NAc), and attenuated NAc expression of delta FosB. There was no effect of either stress or virus on BDNF expression in the prefrontal cortex. Since social stress-induced upregulation of VTA MORs is necessary for consequences of social stress, next activity dependent changes in AKT, a downstream target of MOR stimulation associated with sensitization to psychostimulant drugs, were investigated. Using fluorescent immunohistochemical double labeling for the active form of AKT (pAKT) and markers of either GABA or dopamine neurons in the VTA, it was determined that social stress significantly increased the expression of pAKT in GABA, but not dopamine neurons, and that this effect was dependent on VTA MOR expression. Moreover, intra-VTA inhibition of pAKT during stress prevented stress-induced weight gain deficits, while acute inhibition of VTA pAKT blocked the expression of cross-sensitization in subjects that had previously exhibited sensitized locomotor activity. Together these results suggest that social stress upregulates MORs on VTA GABA neurons, resulting in AKT phosphorylation, and that increased VTA MOR-pAKT signaling may represent a novel therapeutic target for the intervention of substance abuse disorders.
ContributorsJohnston, Caitlin (Author) / Hammer, Ronald P. (Thesis advisor) / Nikulina, Ella M. (Thesis advisor) / Neisewander, Janet L. (Committee member) / Wu, Jie (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2015
Description
The purpose of this study was to evaluate existing data from the Arizona Youth Survey (AYS) to give policymakers and representatives from the Arizona Criminal Justice Commission some insight into the high rates of youth prescription drug abuse. This study examined trends in prescription drug consumption among Pima County, Arizona adolescents, as well as the contexts in which these drugs were used and the numerous consequences resulting from such actions. The results of this research will allow professionals at the Arizona Criminal Justice Commission to inform state officials on the most cost-effective methods of prescription drug abuse prevention and intervention.
ContributorsLewis, Melissa (Author) / Roosa, Mark (Thesis director) / Dumka, Larry (Committee member) / Malone, Shane (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
According to my 2016 survey of ASU undergraduate students, 33% have used stimulant medications (e.g. Adderall or Ritalin) without a prescription to study. I view this practice as a step towards cognitive enhancement, which is the deliberate application of biotechnology to radically alter the human condition. From a foresight perspective, the ability to actively improve human beings, to take our evolutionary destiny into our own hands, may be a turning point on par with agriculture or the use of fossil fuels. The existential risks, however, may be greater than the benefits—and many of the most radical technologies have made little documented progress.
I turn to an actual example where people are trying to make themselves marginally better at academic tasks, as a guide to how future transformative development in human enhancement may be incorporated into everyday practice. This project examines the history and context that led to the widespread use of stimulant medication on college campuses. I describe how Attention Deficit Hyperactivity Disorder (ADHD), for which stimulant medication is prescribed and diverted, governs students, negotiates relationships between parents and school authorities, and manages anxieties resulting from a competitive neoliberal educational system. I extend this archeology of ADHD through the actions and ethical beliefs of college students, and the bioethical arguments for and against human enhancement. Through this work, I open a new space for an expanded role for universities as institutions capable of creating experimental communities supporting ethical cognitive enhancement.
I turn to an actual example where people are trying to make themselves marginally better at academic tasks, as a guide to how future transformative development in human enhancement may be incorporated into everyday practice. This project examines the history and context that led to the widespread use of stimulant medication on college campuses. I describe how Attention Deficit Hyperactivity Disorder (ADHD), for which stimulant medication is prescribed and diverted, governs students, negotiates relationships between parents and school authorities, and manages anxieties resulting from a competitive neoliberal educational system. I extend this archeology of ADHD through the actions and ethical beliefs of college students, and the bioethical arguments for and against human enhancement. Through this work, I open a new space for an expanded role for universities as institutions capable of creating experimental communities supporting ethical cognitive enhancement.
ContributorsBurnam-Fink, Michael (Author) / Miller, Clark (Thesis advisor) / Hurlbut, Ben (Thesis advisor) / Wetmore, Jameson (Committee member) / Arizona State University (Publisher)
Created2016