Matching Items (28)
Filtering by
- Resource Type: Text
Description
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of this study is to investigate the literacy practices of three members of Alcoholics Anonymous (A.A.) and to explore how they use these practices to support and maintain their recovery in their lives. This study also aims to examine how each participant used specialist language, enacted certain identities and acquired the secondary Discourse in A.A. through literacy use. This dissertation study is the result of in-depth interviewing in which each participant was interviewed three times for 90-minutes. These interviews were then transcribed and analyzed using discourse analysis. Study results are presented in three chapters, each one designated to one of the participants. Within these chapters is a life history (chronology) of the participant leading up to the point in which they got sober. The chapters also include a thematic discourse analysis of the interview transcripts across themes of literacy practice and topics in A.A. A conclusion is then presented to investigate how literacy was used from a sociocultural perspective in the study. Due to the emotionally charged nature of this dissertation, it has been formatted to present the stories of the participants first, leaving the theoretical framework, literature review and research methods to be included as appendices to the main text.
ContributorsClausen, Jennifer Ann (Author) / Marsh, Josephine (Thesis advisor) / Hayes, Elisabeth (Committee member) / Serafini, Frank (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
Drug addiction is a pervasive problem in society, as it produces major increases in health care costs, crime, and loss of productivity. With over 3 million long-term users in America alone, cocaine is one of the most identifiable and addictive drugs. Cocaine produces major neurological changes in the central nervous system, including widespread changes in gene expression. MicroRNAs are small, non-coding transcripts that regulate gene expression post-transcriptionally by preventing translation into function protein. Given that one miRNA can target several genes simultaneously, they have the potential to attenuate drug-induced changes in gene expression. We previously found that the microRNA miR-495 regulates several addiction-related genes (ARGs) and is highly expressed in the nucleus accumbens (NAc), an important brain region involved in reward and motivation. Furthermore, acute cocaine decreases miR-495 expression and increases ARG expression in the NAc. Therefore, the aim of this thesis was to determine the effect of miR-495 overexpression in the NAc on cocaine self-administration behavior. Male Sprague Dawley rats were trained to lever press for cocaine and were then infused with a lentivirus into the NAc that either overexpressed green fluorescent protein (GFP, control) or miR-495+GFP. We then tested the rats on several doses of cocaine on both a fixed ratio (5) and progressive ratio (PR) schedule of reinforcement. We performed a follow-up experiment that included the same viral manipulation and testing, but the reinforcer was switched to food pellets. We found that NAc miR-495 overexpression reduces cocaine self-administration on a PR, but not an FR5, schedule of reinforcement. We found no effects of miR-495 overexpression on food reinforcement. These data suggest that NAc miR-495 regulates genes involved in motivation for cocaine, but not general motivation based on the data with food reinforcement. Future studies will seek to determine the specific target genes responsible for our behavioral effects.
ContributorsGalles, Nick (Author) / Neisewander, Janet (Thesis director) / Bastle, Ryan (Committee member) / Foster, M. (Committee member) / Barrett, The Honors College (Contributor)
Created2016-05
Description
While not officially recognized as an addictive activity by the Diagnostic and Statistical Manual of Mental Disorders, video game addiction has well-documented resources pointing to its effects on physiological and mental health for both addict and those close to the addict. With the rise of eSports, treating video game addiction has become trickier as a passionate and growing fan base begins to act as a culture not unlike traditional sporting. These concerns call for a better understanding of what constitutes a harmful addiction to video games as its heavy practice becomes more financially viable and accepted into mainstream culture.
ContributorsGohil, Abhishek Bhagirathsinh (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Computer Science and Engineering Program (Contributor)
Created2015-05
Description
In recent years the abuse of synthetic cathinones, "Bath Salts," has increased. The purpose of this study was to analyze two synthetic cathinones, methylone and α-pvp, for hedonic properties or the potential to be abused. This was tested using an intracranial self-stimulation paradigm, a robust measurement for reward. It was found methylone resulted in an abuse potential similar to MDMA, ecstasy, abuse. Moreover, the results for α-pvp showed a high liability for abuse.
ContributorsJohnson, Craig Trevor (Author) / Olive, Foster (Thesis director) / Presson, Clark (Committee member) / Montesano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
Description
Cocaine is a highly addictive psychostimulant that is widely used around the world. It is far more cost effective to curb this problem through treatment than by any other method as medicinal drug treatment is 15 times more effective than law enforcement at reducing the societal costs of cocaine use as determine by RAND corp. In a previous paper from our lab, it was found that via virally mediated introduction of additional 5-HT1B receptors into the nucleus accumbens there was a leftward shift in the cocaine intake dose-response curve in animals that were self-administering cocaine by pressing a lever. These findings suggest that 5-HT1B receptor action enhances the reinforcing effects of cocaine. However, when animals were given a 21-day period of prolonged abstinence and then tested for cocaine intake, it was determined that 5-HT1B receptor action had the opposite effect of decreasing cocaine intake presumably due to a decrease in the reinforcing effects of cocaine: [16]. The experiment in the current paper was devised to further test this finding via pharmacological means using the 5-HT1B agonist CP 94253 to increase stimulation of 5-HT1B receptors. Animals were trained to self-administer by pressing a lever on fixed ratio schedules of cocaine reinforcement given at 0.75 mg/kg and 0.075 mg/kg doses of cocaine. These doses allowed us to examine changes in self-administration on both the ascending and descending limbs of the inverted u-shaped cocaine dose-effect curve. Our results indicated that in animals given CP 94253 exhibited a decrease in responding on both the ascending and descending limbs of the dose response curve demonstrating a downward shift after prolonged abstinence. These exciting results suggest that the agonist decreases cocaine intake, and therefore, the agonist may be a useful treatment for cocaine dependence.
ContributorsYanamandra, Krishna Teja (Author) / Neisewander, Janet (Thesis director) / Goldstein, Elliott (Committee member) / Pentkowski, Nathan (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
Substance abuse disorders affect 15.3 million people worldwide. The field has primarily focused on dopaminergic drugs as treatments for substance use disorders. However, recent work has demonstrated the potential of serotonergic compounds to treat substance abuse. Specifically, the serotonin 1B receptor (5-HT1BR), a Gi-coupled receptor located throughout the mesocorticolimbic dopamine system, has been implicated in the incentive motivational and rewarding effects of cocaine. Our research suggests that the stimulation of 5-HT1BRs produces different effects at various time points in the addiction cycle. During maintenance of chronic cocaine administration, 5-HT1BR stimulation has a facilitative effect on the reinforcing properties of cocaine. However 5-HT1BR stimulation exhibits inhibitory effects on reinforcement during prolonged abstinence from cocaine. The aim of this study was to examine the possibility of a switch in the functional role of 5-HT1BRs in the locomotor effects of cocaine at different time points of chronic cocaine administration in mice. We found that the 5-HT1BR agonist CP 94,253 increased locomotor activity in mice tested one day after the last chronic cocaine administration session regardless of whether the chronic treatment was cocaine or saline and regardless of challenge injection (i.e., cocaine or saline). Yet after abstinence, CP 94,253 induced a decrease in locomotor activity in mice challenged with saline and attenuated cocaine-induced locomotion relative to cocaine challenge after vehicle pretreatment. These findings suggest that a switch in the functional role of 5-HT1BR is observed at different stages of the addiction cycle and further suggest that clinical applications of drugs acting on 5-HT1BR should consider these effects.
ContributorsBrunwasser, Samuel Joshua (Author) / Neisewander, Janet (Thesis director) / Pentkowski, Nathan (Committee member) / Der-Ghazarian, Taleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2014-05
Description
The main objective of the research was to gather as much information and arguments about why we need to end the war on drugs and put them into one piece of work that was compelling and thorough, but also concise. This goal was achieved through first explaining how addiction is strongly related to the environment around the addict and whether they have adequate tools to bond with those around them. After coming to the conclusion that the war on drugs has been a failure and is misunderstood by most people, the strategy for legalization of recreational drugs was outlined as well as the economic, social, and health benefits of pursuing that strategy. The conclusion is that while the war on drugs has good intentions, it has been largely ineffective and imposed cruel punishments on addicts that end up causing more harm than they prevent, it is time to move forward and legalize all recreational drug use with licensed sales, harm reduction programs, and proper education to create a more effective strategy of preventing drug use and the harm it brings.
ContributorsArndt, Nicholas Brandon (Author) / Koretz, Lora (Thesis director) / Kashiwagi, Jacob (Committee member) / W. P. Carey School of Business (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Nicotine use is an outstanding public health problem with associated social and economic consequences. Nicotine is an active alkaloid compound in tobacco and is recognized as a psychoactive drug. Preclinically, nicotine addiction and relapse can be modeled using a self-administration-reinstatement paradigm. Here, we used a nicotine self-administration and contingent cue-induced reinstatement model to examine rapid, transient synaptic plasticity (t-SP) induced by nicotine cue-triggered motivation. Although preliminary, treatment with the NMDA GluN2B subunit antagonist, ifenprodil, reduced reinstated nicotine seeking, and increased the percentage of spines with smaller head diameters. Thus, future studies are needed to fully parse out the role of NAcore GluN2B receptors in cued nicotine seeking and t-SP.
ContributorsMccallum, Joseph John (Author) / Gipson-Reichardt, Cassandra (Thesis director) / Neisewander, Janet (Committee member) / Olive, Michael Foster (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05