Browsing by Subject "Addiction"

Problem gambling, a fairly recent addition to the Diagnostic and Statistical Manual of Mental Disorders, is estimated to affect between two and five percent of the US adult population (Volberg 2001). While present in all racial groups, this disorder is not evenly distributed, as Blacks are more likely than any other group to become problem gamblers (Welte et al. 2006). And while this pattern is consistent with those found with other disorders (Black 1984; Ford and Widiger 1989; Strakowski et al. 1993), it is important to note that thirty years ago, when the first study of problem gambling prevalence was conducted and the disease had only recently been institutionalized, there was no difference in rate of illness by race (Kallick et al. 1979). This dissertation aims to explore this phenomenon: the role of race in the making of problem of gambling.

Through a multi-site and multi-method approach, this study examines the assumed race neutrality of gambling addiction. By tracing the history of gambling policy and North Carolina's adoption of a lottery program, this study explores how the state further defined problem gambling as a mental illness. Following this, participant observation of state-sponsored problem gambling counselor training workshops provides insight into the ways racialized understandings of behavior are constructed and maintained through counselor education. To gain a sense of how gambling is lived, this study involves participant observation of lottery gambling in convenience stores to interrogate racialized conceptions of behavior and reveal how financial gain motivates gambling across groups.

Opioid drug abuse represents a serious public health concern with few effective therapeutic strategies. A primary goal for researchers modeling substance abuse disorders has been the delineation of the biological and environmental factors that shape an individual’s susceptibility or resistance to the reinforcing properties of abused substances. Early-life environmental conditions are frequently implicated as critical mediators for later-life health outcomes, although the cellular and molecular mechanisms that underlie these effects have historically been challenging to identify. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation in the nucleus accumbens (NAc), and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10). The experiments described in this dissertation were thus designed to address if inflammatory signaling in the NAc may underlie the effects of early-life experience on later-life opioid drug-taking. The results demonstrate that neonatal handling attenuates intravenous self-administration of the opioid remifentanil in a drug concentration-dependent manner. Transcriptional profiling of the NAc reveals a suppression of pro-inflammatory cytokine and chemokine signaling molecules and an increase in anti-inflammatory IL-10 in handled rats following repeated exposure to remifentanil. To directly test the hypothesis that anti-inflammatory signaling can alter drug-taking behavior, bilateral intracranial injections of plasmid DNA encoding IL-10 (pDNA-IL-10) or control pDNA were delivered into the NAc of naïve rats. pDNA-IL-10 treatment reduces remifentanil self-administration in a drug concentration-dependent manner, similar to the previous observations in handled rats. Additional experiments confirmed that neither handling nor pDNA-IL-10 treatment alters operant responding for food or sucrose rewards. These results help define the conditions under which ventral striatal neuroimmune signaling may influence motivated behaviors for highly reinforcing opioid drugs.

This dissertation explores the ways in which British popular novels of the eighteenth century functioned as commodities. "Novel Addiction", the title of this dissertation has a double meaning: Addiction was a new conceptual framework developed during the eighteenth century in order to manage the increasing anxiety brought upon the culture of consumption, and the novel, one of the most popular commodities of the same period, was addictive. Both as successful commodities and efficient cultural agents, popular novels that were categorized as the sentimental or the gothic participated in the process of creating and disseminating models of addiction that warranted perpetual discipline. However, this discipline does not aim at preventing or eliminating addiction. It rather manages addiction as "habit" in a way that guarantees proliferation of the market economy. By employing the framework of addiction, I intend to reconfigure the role of the novel in the construction of individual and collective models of consumption-oriented subjectivity.

The first chapter begins with Eliza Haywood's Present for Women Addicted to Drinking where the author proposes novel-reading as the best cure for alcohol addiction, which allows me to explore a parallel between the phenomenon called the "gin craze" and the proliferation of print commodities. The second and third chapter discuss the sentimental novel and the gothic novel respectively focusing on the characteristics of each genre that make them addictive. The fourth and final chapter discusses Jane Austen's Northanger Abbey and Sense and Sensibility, which address and attempt to manage "novel addiction," a problem posed by the popular novels of her contemporaries.

Abstract

Wesley’s systemic model of discipleship through Societies, Bands, and Classes provides the foundation for a uniquely Wesleyan model of recovery. John Wesley’s early methods of psyches therapeia, “a spiritually-based psychotherapeutic method for healing the human soul and producing real soul-change” is still relevant today and is a proven method for transformation as is evidenced in both the Holy Club, the Oxford Group, and Alcoholics Anonymous.

Addiction is known to cross all ethnic, gender, and socio-economic lines. Addiction permeates and affects every segment of society. Today addiction extends beyond drugs and alcohol and can include many other deeds, actions, and conduct. Despite the widespread proliferation of addiction, it has traditionally been relegated to the shadows as a topic of conversation. What is conspicuously absent in most conversations involving addiction is any mention of the church and its role in the process of rehabilitation and recovery.

This is surprising given the clarity of Jesus’ mission as defined in Luke 19:10, “For the Son of Man came to seek out and to save the lost.” Rather than live out the messy incarnate mission and message of Jesus Christ “to seek and to save the least and the lost,” the church has remarkably outsourced recovery to drug and alcohol rehabilitation centers. The church, for the most part, has relinquished any role it might play in recovery to secular players, and in doing so, a much-needed voice on the topic of recovery has been silenced. In remaining silent and abdicating it’s calling, the church has forced persons to rely on mere behavioral modification programs. As a result, recovery programs advocate sobriety from a substance or behavior without addressing the real need for change and transformation of the soul itself. Consequently, one’s current addiction is frequently exchanged for a different one. Programs that do not treat addiction at a spiritual level will continue to graduate participants that simply trade one addiction for another, and this will continue until the underlying issues of sin, brokenness, attachment, and denial are appropriately and thoroughly addressed.

The United Methodist Church and its congregations do not know how to effectively address issues of addiction and recovery within a Wesleyan framework. Consequently, the United Methodist family is left to use recovery materials developed by other denominations that simply do not match the ethos, culture, and theology of the United Methodist Church. Restoration: A Wesleyan Model of Recovery seeks to rectify this and offer a unique Methodist resource, to be used as a means of salvation and healing based upon the rich culture and heritage of the people called Methodist. The text is supported by an abundance of resources including videos, sermons, and a daily workbook.

Learning and memory are mediated by changes in synaptic and neuronal function within brain circuits, and is supported by dynamic waves of stimulus-dependent transcription in the nucleus of neurons. Stimulus-dependent transcription relies heavily on the epigenetic landscape of a given neuron, which is highly cell-type specific and can be further tuned by experience. Developments in genetic tools and methods to survey the entire transcriptome and epigenome have increased our ability to study stimulus-dependent transcription in diverse cell-types, including rare populations of interneurons. Application of these tools to addiction models, where long-lasting changes in behavior depend on stimulus-dependent transcription in diverse cell-types in multiple areas of the corticomesolimbic reward circuit, presents a particularly potent opportunity to increase our understanding of the functional consequences of stimulus-dependent transcription in diverse cell-types in a system that is highly relevant to human health. In the nucleus accumbens (NAc), parvalbumin-expressing (PV+) interneurons exert strong control over local circuit output and downstream behavior, including behavioral responses to drugs of abuse. Recent data from our lab suggest that perineuronal net (PNN) genes are a promising target for behaviorally-relevant, drug-dependent functional adaptations in this rare cell-type. In this dissertation, I use histological techniques in mouse tissue to validate in situ the heterogeneous transcriptional regulation of NAc PV+ interneurons and specific cell adhesion gene targets in response to psychostimulants, and explore the developmental and drug-dependent regulation of PNNs and the PNN gene Bcan. I use genetic and viral tools to specifically knockdown Bcan expression in NAc PV+ cells, and demonstrate that Bcan stabilizes their excitatory synaptic inputs even in adulthood and restricts the development of cocaine-context associations, showing that NAc PV+ interneurons and their PNNs play an important role in limiting the development of addiction-related behaviors. Finally, I use dCas9-mediated epigenetic editing to tune activity-dependent transcription of select rapid primary response genes, which are thought to interact with cell-type and cell-state dependent chromatin to coordinate later waves of stimulus-dependent transcription. I show that the fine details of activity-dependent transcription of rapid primary response genes resulting from chromatin state can lead to physiological changes in protein, and downstream neural physiology and behavior.

The epigenome underlies cell type and state and in post-mitotic neurons, and it regulates the ability for rapid response to activity. Since neurons exit the cell cycle early in development and are long lived, remodeling of brain function requires that neurons show transcriptional plasticity to let then change in function in response to stimuli including psychostimulants and developmental cues. This response is driven by the epigenomic regulation in a cell-type-specific manner. Many studies assessing experience driven genomic responses have been carried out in bulk tissues so cell-type-specific genomic responses to stimuli that drive neuronal plasticity remains poorly understood. To understand the epigenomic and transcriptomic mechanisms driving neuronal plasticity, here we study multi-omic genomic data from two contexts in the mouse brain: 1) psychostimulant responses in the nucleus accumbens and 2)the postnatal and postmitotic maturation of developing cerebellar granule neurons. In both systems, I implemented integrative bioinformatic approaches to predict transcription factor (TF) activity in regulating the transcriptome. I elucidated cell-type-specific amphetamine induced transcriptomic responses, identified canonical activity regulated transcription factors regulating those responses, and determined collaborators and developmental targets of the Zic family TFs, revealing novel roles of Zics regulating migration and synaptic maturation in CGN development. The studies reveal novel mechanistic insights into neuronal plasticity in different neuronal cell types by using integrative computational approaches to model chromatin topology, chromatin accessibility, gene expression, and TF binding.