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Catharanthine Modulates Mesolimbic Dopamine Transmission: A Potential Treatment For Alcohol Use Disorder, Benjamin M. Williams
Catharanthine Modulates Mesolimbic Dopamine Transmission: A Potential Treatment For Alcohol Use Disorder, Benjamin M. Williams
Theses and Dissertations
Catharanthine is derived from the Catharanthus roseus plant and is an analog to ibogaine, a drug that reduces opioid and alcohol withdrawal symptoms and decreases drug self-administration in both animals and humans. Catharanthine has promise to be an alternative pharmacological treatment for addiction without the adverse side effects associated with ibogaine. The objective of this study was to evaluate catharanthine’s effects on dopamine (DA) transmission in the mesolimbic DA system as well as determine its effects on both ethanol withdrawal induced anxiety and drug-seeking behaviors in mice. We hypothesized that catharanthine would inhibit evoked DA release in the nucleus accumbens …
The Effects Of Alcohol On Bdnf And Cd5 Dependent Pathways, Andrew Jordan Payne
The Effects Of Alcohol On Bdnf And Cd5 Dependent Pathways, Andrew Jordan Payne
Theses and Dissertations
Alcohol represents the third leading cause of preventable death in the United States. Yet, despite its prevalent role in impeding human health, there is much to understand about how it elicits its effects on the body and how the body and brain change when an individual becomes physiologically dependent upon alcohol. The work presented herein represents an effort to elucidate the acute and chronic effects of alcohol on the nervous system. We investigate two specific protein pathways and their role in alcohol's effects on the body. The first begins with brain-derived neurotrophic factor (BDNF), which acts on TrkB, and ends …
Alcohol Affects The Reward Pathway Of The Brain Via A6-Containing Nicotinic Acetylcholine Receptors In The Nucleus Accumbens, Elizabeth Qiufeng Anderson
Alcohol Affects The Reward Pathway Of The Brain Via A6-Containing Nicotinic Acetylcholine Receptors In The Nucleus Accumbens, Elizabeth Qiufeng Anderson
Theses and Dissertations
The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system consisting of DA neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc) underlies the rewarding properties of ethanol (EtOH) and nicotine (NIC). Although the dogma is that EtOH enhancement of DA neural activity contributes to enhancement of DA transmission, DA neurons are not sensitive to rewarding levels of EtOH. However, VTA GABA neurons are sensitive to low-dose EtOH. We have shown previously that EtOH modulation of DA release in the NAc is mediated by α6-containing nicotinic receptors (α6*-nAChRs), that α6*-nAChRs mediate …
Aerobic Exercise Alters Opioid Receptors Following Chronic Alcohol Exposure, James N. Brundage
Aerobic Exercise Alters Opioid Receptors Following Chronic Alcohol Exposure, James N. Brundage
Theses and Dissertations
Opioid receptors have been a target of pharmacological manipulation in alcohol use disorder (AUD) recovery protocols for many years. Aerobic exercise, a common adjunct in AUD recovery, is known to modulate opioid receptors (ORs) both during both acute and long term exposure. The three subtypes of ORs: mu (MOR), delta (DOR), and kappa (KOR) are all expressed on neurons in the mesocorticolimbic circuitry. Kappa-opioid receptors are expressed directly on dopamine (DA) neuron terminals in the nucleus accumbens (NAc). Mu and Delta ORs are expressed on cholinergic interneurons (CINs) and GABA neurons in the NAc. In alcohol dependent rodents, KORs are …
Mechanoreceptor Activation In The Treatment Of Drug-Use Disorders: Mechanism And Outcome, Kyle Bills
Mechanoreceptor Activation In The Treatment Of Drug-Use Disorders: Mechanism And Outcome, Kyle Bills
Theses and Dissertations
The therapeutic benefits attributed to activation of peripheral mechanoreceptors are poorly understood. There is growing evidence that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) that are outside the canonical somatosensory circuits. This work demonstrates that activation of peripheral mechnoreceptors via mechanical stimulation (MStim) is sufficient to increase dopamine release in the nucleus accumbens (NAc), alter neuron firing rate in the ventral tegmental area (VTA) and increase membrane translocation of delta opioid receptors (DORs) in the NAc. Further, we demonstrate that these effects are dependent on DORs and acetylcholine receptors. Additionally, MStim can block neuronal markers of …
Neuroimmune-Mediated Alcohol Effects On Ventral Tegmental Area Microglia And Infiltrating Leukocytes, Travis Jonathan Clarke
Neuroimmune-Mediated Alcohol Effects On Ventral Tegmental Area Microglia And Infiltrating Leukocytes, Travis Jonathan Clarke
Theses and Dissertations
Microglia are the primary immune cell in the central nervous system and are known as the “resident” macrophages in the central nervous system (CNS). While microglia are classically known as the immune cells of the CNS, their role has more recently been shown to extend far beyond immunity. The effects of ethanol on the brain are closely linked to neuroimmune responses mediated by microglia that are present in the healthy brain from the time of development. Though microglia have been classified as the “resident” immune cells of the CNS, new research suggests that other immune cells may be implicated in …
Neuroimmune-Mediated Alcohol Effects On Ventral Tegmental Area Neurons, Stephanie Bair Williams
Neuroimmune-Mediated Alcohol Effects On Ventral Tegmental Area Neurons, Stephanie Bair Williams
Theses and Dissertations
Dopamine (DA) transmission is a key player in the rewarding aspects of ethanol as well as ethanol dependence. The current dogma is that DA transmission is increased during ethanol via the inhibition of ventral tegmental area (VTA) GABA neurons and that excitation of VTA GABA neurons during withdrawal results in decreased DA transmission. Microglia, the major neuroimmune effector in the brain, may be a key mediator in this process by releasing cytokines following activation. We evaluated the effect of ethanol on cytokine concentrations in the VTA and NAc using a cytometric bead array, and found that low dose ethanol (1.0 …
“One More Drinkin’ Song”: A Longitudinal Content Analysis Of Country Music Lyrics Between The Years 1994 And 2013, Keith Mckay Evans
“One More Drinkin’ Song”: A Longitudinal Content Analysis Of Country Music Lyrics Between The Years 1994 And 2013, Keith Mckay Evans
Theses and Dissertations
The lyrical content of pop music has rarely been studied, particularly for country music. The lyrics of the top 50 country songs for each year between 1994 and 2013 were coded for violent, sexual and substance use-related content. Violence had increased, as had sexual references, substance use, and substance use associated with sexual activity. Of particular note is the frequency of references to alcohol; 21% of the 1,000-song sampling frame contained alcoholic references, and the average for the final five-year period (2009-2013) was 1.01 references per song. This research should serve as a springboard into further studies about the lyrical …
Predicting Alcohol Consumption In Adolescent Rhesus Macaques (Macaca Mulatta), Andrea Nichole Sorenson
Predicting Alcohol Consumption In Adolescent Rhesus Macaques (Macaca Mulatta), Andrea Nichole Sorenson
Theses and Dissertations
Numerous studies show that a low level of response to the intoxicating effects of alcohol is considered a risk factor for future alcoholism. However, assessing this sensitivity usually requires administering a controlled dose of alcohol, which has a number of inherent problems. Early observations in our lab suggest that the response to anesthetics that show cross tolerance with alcohol, like ketamine, are blunted in nonhuman primates at risk for high alcohol intake, and may be a viable measure of future alcohol consumption. This study was designed to test potential predictors of future alcohol consumption using the change in ketamine across …
Adolescent Interest In Alcohol Responsibility Messages: The Message Matters, Kevin Kimball John
Adolescent Interest In Alcohol Responsibility Messages: The Message Matters, Kevin Kimball John
Theses and Dissertations
Adolescents are especially vulnerable to image-based messages, which place them directly in line with the lifestyle messages presented in numerous alcohol advertisements. Research has shown that teenagers encounter alcohol advertisements from a variety of sources, prompting concern over the consequences of exposure and the risks associated with teen drinking. Warning messages contained within these alcohol advertisements are often vague in their wording and targeted to promote responsible drinking among adults, making them wholly inadequate for teen deterrence. This thesis explores the problems with current alcohol responsibility messages when dealing with teens, and proposes the development of new, modified messages, that …
The Role Of Connexin-36 Gap Junctions In Alcohol Intoxication And Reward, Kathryn Diane Bradley
The Role Of Connexin-36 Gap Junctions In Alcohol Intoxication And Reward, Kathryn Diane Bradley
Theses and Dissertations
The purpose of this thesis project was to examine the function of connexin-36 (Cx36) gap junctions (GJs) in producing alcohol's intoxicating and rewarding effects. GABA neurons are thought to inhibit dopamine (DA) neurotransmission in the mesocorticolimbic system, which originates in the midbrain ventral tegmental area (VTA) and projects to limbic structures such as the nucleus accumbens (NAcc). The mesolimbic DA system is believed to be the neural substrate of alcohol intoxication and addiction (Tepper, Paladini, & Celada, 1998). Alcohol suppresses the firing rate of GABA neurons in the VTA (Gallegos, Criado, Lee, Henriksen, & Steffensen, 1999) and presumably disinhibits DA …
Altered States Of Style: The Drug-Induced Development Of Jack Kerouac's Spontaneous Prose, Eric M. Izant
Altered States Of Style: The Drug-Induced Development Of Jack Kerouac's Spontaneous Prose, Eric M. Izant
Theses and Dissertations
Jack Kerouac's spontaneous prose method was inspired in part by his use of drugs while writing. While there is abundant biographical evidence that Kerouac used drugs frequently, little attention has been paid to their effects on the development of his style. This thesis attempts to demonstrate that the altered states of consciousness produced by Kerouac's drug use should be considered in conjunction with historical, cultural, and biographical forces in tracing the evolution of Kerouac's creative growth. As a member of the Beat Generation, Kerouac used drugs both as a social statement of rebellion and for artistic insight. In fact, he …
Neuronal And Molecular Adaptations Of Gaba Neurons In The Ventral Tegmental Area To Chronic Alcohol, Kimberly Hales
Neuronal And Molecular Adaptations Of Gaba Neurons In The Ventral Tegmental Area To Chronic Alcohol, Kimberly Hales
Theses and Dissertations
The purpose of this thesis project was to examine the effects of chronic alcohol on the excitability and molecular adaptation of GABA neurons of the ventral tegmental area (VTA). GABA neurons are of interest with regards to ethanol intoxication, reinforcement, and dependence due to their widespread distribution and connectivity to mesocorticolimbic dopamine (DA) neurons implicated in alcohol reward and addiction. Since we have previously shown adaptation of VTA GABA neuron firing rate to chronic ethanol (Gallegos, Criado et al. 1999) and suppression of gap-junction (GJ) mediated coupling between these neurons by acute ethanol (Stobbs, Ohran et al. 2004), we wanted …
Sibling Influence On Adolescent Cigarette, Alcohol, And Marijuana Use, Benjamin G. Gibbs
Sibling Influence On Adolescent Cigarette, Alcohol, And Marijuana Use, Benjamin G. Gibbs
Theses and Dissertations
The purpose of this study is to estimate the association between sibling drug use and adolescent alcohol, cigarette, and marijuana use. Research is conducted using survey data from a probability sample of 4,987 adolescents in grades 9–12 in Utah. To account for the limited frequency of drug use among respondents, Poisson regression is used to estimate models for each type of drug. In support of current literature, findings indicate that having a sibling who uses drugs increases the frequency of drug use substantially, even when peer influences are taken into account. Significant sibling associations with adolescent drug use found in …