Substance Abuse and Addiction Commons^™

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations & Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Innovative Virtual Wellness Interventions At An Academic Medical Center: A Pilot Feasibility Study, Ritika Baweja, Michael Hayes, Aditya Joshi, Raman Baweja

Journal of Wellness

Introduction: There is generally a concerning likelihood of burnout in healthcare workers. Given the impact of COVID-19 on healthcare workers, our institution identified the need for wellness interventions to foster adaptive functioning and mitigate burnout. The purpose of this pilot project was to assess the feasibility of virtual holistic interventions like meditation, art, laughter therapy and dance and their impact on overall well-being of physicians and advanced practice providers (APPs).

Methods: A series of 12 virtual sessions (art therapy, dance therapy, mindfulness-based practices/meditation and laughter therapy) were offered to providers over a 6-month period. Participants completed an online survey reporting …

Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

No abstract provided.

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Drug Ideologies Of The United States, Macy Montgomery

Helm's School of Government Conference - American Revival: Citizenship & Virtue

The United States has been increasingly creating lenient drug policies. Seventeen states and Washington, the District of Columbia, legalized marijuana, and Oregon decriminalized certain drugs, including methamphetamine, heroin, and cocaine. The medical community has proven that drugs, including marijuana, have myriad adverse health side effects. This leads to two questions: Why does the United States government continue to create lenient drug policies, and what reasons do citizens give for legalizing drugs when the medical community has proven them harmful? The paper hypothesizes that the disadvantages of drug legalization outweigh its benefits because of the numerous harms it causes, such as …

Du Undergraduate Showcase: Research, Scholarship, And Creative Works, Caitlyn Aldersea, Justin Bravo, Sam Allen, Anna Block, Connor Block, Emma Buechler, Maria De Los Angeles Bustillos, Arianna Carlson, William Christensen, Olivia Kachulis, Noah Craver, Kate Dillon, Muskan Fatima, Angel Fernandes, Emma Finch, Colleen Cassidy, Amy Fishman, Andrea Francis, Stacia Fritz, Simran Gill, Emma Gries, Rylie Hansen, Shannon Powers, Jacqueline Martinez, Zachary Harker, Ashley Hasty, Mykaela Tanino-Springsteen, Kathleen Hopps, Adelaide Kerenick, Colin Kleckner, Ci Koehring, Elijah Kruger, Braden Krumholz, Maddie Leake, Lyneé Alves, Seraphina Loukas, Yatzari Lozano Vazquez, Haley Maki, Emily Martinez, Sierra Mckinney, Mykaela Tanino-Springsteen, Audrey Mitchell, Kipling Newman, Audrey Ng, Megan Lucyshyn, Andrew Nguyen, Stevie Ostman, Casandra Pearson, Alexandra Penney, Julia Gielczynski, Tyler Ball, Anna Rini, Christina Rorres, Simon Ruland, Helayna Schafer, Emma Sellers, Sarah Schuller, Claire Shaver, Kevin Summers, Isabella Shaw, Madison Sinar, Claudia Pena, Apshara Siwakoti, Carter Sorensen, Madi Sousa, Anna Sparling, Alexandra Revier, Brandon Thierry, Dylan Tyree, Maggie Williams, Lauren Wols

DU Undergraduate Research Journal Archive

DU Undergraduate Showcase: Research, Scholarship, and Creative Works

Comparative Analysis Of The Effects Of Actual Versus Assumed Opioid Experience On The Regulation Of Ventral Striatal Opioid Receptor Gene Expression, Indu Mithra Madhuranthakam, Martin Job

Rowan-Virtua Research Day

Rationale: We conducted experiments to assess the effect of prior opioid experience on gene expression changes. We compared the current experimenter-imposed short versus extended-access conditions of opioid self-administration and developed a new quantitative method to determine their effectiveness in identifying the role of opioid experience in regulating opioid receptor expression levels in the ventral striatum (VS) using an oxycodone self-administration/abstinence model.

Methods: In this study, male Sprague-Dawley rats (n=36) were trained for 20 days to self-administer oxycodone at 0.1 mg/kg/infusion under short access (n=15, or saline as controls n=3, for 3h/day) or extended access (n=15, or saline as controls n=3, …

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

The Effects Of Extended Fructose Access On Relative Value And Demand For Fructose, Saccharin, And Ventral Tegmental Stimulation, Megan Halloran

Theses and Dissertations--Psychology

Globally, food addiction (FA) is a growing area of research and is largely attributed to the availability of foods that are both energy dense and high in fats and sugars. Further, it has been suggested, that sugar and fat, when consumed frequently, have properties similar to drugs of abuse. While the validity of FA is questioned, researchers have drawn parallels between substance use disorder (SUD) and FA. For example, sugar binge models emphasize craving, withdrawal and binging as primary components of FA, which are also hallmarks of SUD. Additionally, both natural rewards, like sugars, and drug rewards act on the …

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone

Theses and Dissertations--Psychology

Evidence suggests that rats given long access (LgA) sessions to self-administer (SA) opioids escalate their intake, while also showing greater withdrawal severity and drug-induced reinstatement compared to rats maintained on short access (ShA) daily SA sessions. Little is known about the neural changes that occur during opioid escalation that may impact withdrawal and relapse. Past work examining opioid SA using ShA sessions in rodents has identified the central amygdala (CeA) as an area of interest that becomes hyperactive in acute withdrawal and may be involved in the incubation of craving that occurs after protracted withdrawal. However, these studies have not …

Individual Differences In Lpp Amplitude And Theta Power Predict Cue-Induced Eating During A Cued Food Delivery Task, Kyla Gibney

Dissertations & Theses (Open Access)

Due to individual differences in the brain’s reward system, some individuals are more vulnerable than others to maladaptive, reward-seeking behaviors, such as substance use or compulsive eating. A body of research has demonstrated that individuals who attribute higher levels of incentive salience to reward-associated cues than to pleasant images (termed “C>P group” throughout) are more vulnerable to compulsive eating than those who attribute higher incentive salience to pleasant images than reward- associated cues (P>C group). Meanwhile, a separate body of research has demonstrated that cognitive control also regulates eating by enabling top-down attentional control. This dissertation aims to …

Association Of Hypomagnesemia And Liver Injury, Role Of Gut-Barrier Dysfunction And Inflammation: Efficacy Of Abstinence, And 2-Week Medical Management In Alcohol Use Disorder Patients., Evan J. Winrich, Khushboo S. Gala, Abhas Rajhans, Christian D. Rios-Perez, Amor J. Royer, Zarlakhta Zamani, Ranganathan Parthasarathy, Luis S. Marsano-Obando, Ashutosh J. Barve, Melanie L. Schwandt, Vatsalya Vatsalya

Faculty Scholarship

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients …

Associations Between Cannabis, Psychosis, And Schizophrenia In Adolescents, Lauren Moment

Academic Leadership Journal in Student Research

The effects of cannabis use on the brain, mind, and body have been studied for decades. The developing brain, particularly the adolescent and young adult brain, undergoes critical development that makes it especially susceptible to the effects of cannabis use. Among the adverse effects of cannabis use in adolescence and young adulthood, psychosis and psychotic disorders (e.g., schizophrenia) have been examined. The association of cannabis use with schizophrenia was first elucidated in a Swedish study of army conscripts. Specifically, conscripts reported their cannabis use exposure and were followed longitudinally to assess the emergence of schizophrenia. The authors found that those …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Role Of The G Protein Beta Gamma Subunits In Serotonin Transporter Dynamics, Nora Awadallah

Dissertations, Theses, and Capstone Projects

Serotonin is a vital neurotransmitter and hormone with significant roles in almost every organ system. In the central nervous system, serotonin mediates physiological functions that in turn guide behavior and mood. Here, serotonin is released from serotonergic neurons and exerts its effects through serotonin receptors. Regulation of serotonin neurotransmission is important for the maintenance of its physiological functions; thus, extracellular serotonin must be sequestered to limit the intensity and duration of serotonin transmission. Disproportionate transmission is strongly linked with neurological and psychiatric ailments.

Extracellular serotonin levels are primarily mediated by the serotonin transporter (SERT), a critically important plasma membrane protein …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

Opioids exert their abuse-related effects by enhancing dopamine (DA) neurotransmission within the brain’s mesolimbic reward system, a neural projection involving DA neurons in the ventral tegmental area (VTA) that project to medium spiny neurons within the nucleus accumbens (NAc). Mu (MOR) are expressed by several populations of GABAergic neurons that tonically inhibit VTA DA neurons. By inhibiting these GABAergic neurons in a MOR-dependent manner, opioids indirectly enhance DA neurotransmission via disinhibition of DAergic neurons. Accumulating evidence indicates that selective pharmacological antagonism of the dopamine D3 receptor (D3R) attenuates the abuse-related effects of several opioids, but the neurobiological mechanisms mediating this …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Examining The Perspectives And Experiences Of Nutrition Educators Working With Clients In Substance Use Recovery Settings, Cora Teets, Paula Plonski, Omolola Adedokun, Heather Norman-Burgdolf

Dietetics and Human Nutrition Faculty Publications

Substance use disorder (SUD) is one of the most detrimental health, social, and economic problems in the United States. Limited studies suggest providing tailored nutrition education during SUD treatment correlates with positive recovery outcomes. The University of Kentucky Nutrition Education Program conducted two focus group sessions to explore and determine educators’ instructional and programmatic needs who deliver nutrition education to clients in substance use recovery throughout Kentucky. The study team identified four emerging themes and several subthemes related to Nutrition Education Program educators working with clientele in recovery. The four emerging themes included: (1) current experiences working with the audience, …

Wellness Review 2021, Part 2, Brian A. Ferguson, Martin Huecker

Journal of Wellness

Introduction: This article presents Part 2 of the biannual JWellness Review of literature from 2021 (July – December). We emphasize new science and resilience initiatives published outside of JWellness that seek understanding of burnout and thriving among healthcare professionals (HCPs).

Methods: For the interval of July 1 to December 30, 2021, PubMed was queried for empirical and observational research studies, review articles, guideline summaries, letters, and editorials. Of 93 results, we reviewed methods and salient points to arrive at a final list of 48 articles for inclusion.

Literature in Review: Common themes that emerged included teamwork, EMR optimization, group decompression, …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …

Whole-Body Vibration Alleviates Symptoms Of Morphine Withdrawal, Gavin C. Jones, Dallin Z. Otteson, Christina A. Small, Taylor Purcell, Nathaniel Hill, Tyler Alger, Arren Hill, David W. Sant, Scott C. Steffensen, Kyle B. Bills

Annual Research Symposium

Whole-body vibration at 80 Hz has previously been shown to blunt neuropathological markers and behavioral symptoms of alcohol dependence. Here, we evaluate its ability to ameliorate symptoms of morphine use and withdrawal. Behavioral and neurophysiological symptoms of withdrawal were reduced significantly by whole-body vibration treatment.