Life Sciences Commons^™

Decision-Making In Rats: Effects Of Drug Abuse, Safa Binte Hossain

Open Access Theses & Dissertations

Decision-making is a critical cognitive function, often impaired by substance abuse. Understanding the underlying mechanisms in both human and animal models is essential for developing effective treatments. This thesis aims to study approach-avoid decision-making in rats and focuses on the impacts of oxycodone self-administration and alcohol abuse on approach-avoid decision-making.We hypothesize that oxycodone self-administration will alter decision-making in female rats, revealing sex differences and distinct psychometric functions, alcohol habituation will similarly affect decision-making in male rats. The study involved 23 Long Evans rats (11 males and 12 females) for decision-making behavioral study connecting multiple levels of rewards and costs combinations. …

Prenatal Alcohol Exposure Induces Anatomical Changes In The Mouse Somatosensory Cortex., Zahra Saad Siddiqui

Dartmouth College Master’s Theses

Atypical tactile responses are implicated in Fetal Alcohol Spectrum Disorders (FASD). Our lab reported diminished tactile sensitivity in young adolescent mice with a history of prenatal alcohol exposure (PAE). Here, I employed immunohistochemistry to investigate the anatomical correlates of altered tactile sensitivity observed in mice with PAE. Using our 3-day binge paradigm, I examined changes in the distribution pattern of pre- (thalamocortical afferents) and postsynaptic (pyramidal neurons) partners involved in processing tactile information in the SSC of Postnatal day (P) 7 mice. In rodents, tactile information is relayed somatotopically to the SSC via TC afferents expressing vesicular glutamate transporter 2 …

Advances And Challenges In Conventional And Modern Techniques For Halal Food Authentication: A Review, Ifrah Usman, Saima Sana, Muhammad Afzaal, Ali Imran, Farhan Saeed, Aftab Ahmed, Yasir Abbas Shah, Muniba Munir, Huda Ateeq, Atka Afzal, Iqra Azam, Afaf Ejaz, Gulzar Ahmad Nayik, Mahbubar Rahman Khan

Faculty and Staff Publications

Food is one of the most necessary needs since human civilization. For Muslims, it is mandatory to consume halal food. From a halal authentication perspective, adulteration of food products is an emerging challenge worldwide. The demand for halal food consumption has resulted in an ever-increasing need for halal product validity. In the market, there are several food products in which actual ingredients and their source are not mentioned on the label and cannot be observed by the naked eye. Commonly nonhalal items include pig derivatives like lard, pork, and gelatin derivatives, dead meats, alcohol, blood, and prohibited animals. Purposely, various …

Serum Biomarker Signature Is Predictive Of The Risk Of Hepatocellular Cancer In Patients With Cirrhosis, Hashem El-Serag, Fasiha Kanwal, Jing Ning, Hannah Powell, Saira Khaderi, Amit G Singal, Sumeet Asrani, Jorge A Marrero, Christopher I Amos, Aaron P Thrift, Michelle Luster, Abeer Alsarraj, Luis Olivares, Darlene Skapura, Jenny Deng, Emad Salem, Omar Najjar, Xian Yu, Hao Duong, Michael E Scheurer, Christie M Ballantyne, Salma Kaochar

Student and Faculty Publications

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study.

METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Sex, Drugs, And Tbi: The Effects Of Sex Hormones And Trkb Activation On Alcohol-Related Behavior Following A Traumatic Brain Injury, Robin B. Oliverio

Graduate Theses, Dissertations, and Problem Reports

Traumatic brain injury (TBI) and alcohol use disorder (AUD) exhibit a bidirectional relationship: AUD increases the risk of incurring a TBI and, inversely, a history of TBI increases the risk of future AUD. The second portion of this relationship has not been as thoroughly investigated. Our lab previously demonstrated that a juvenile TBI significantly increases alcohol self-administration in females compared to uninjured females and the injured females developed a conditioned place preference (CPP) for ethanol. Given this stark sex difference, this dissertation will examine the mechanism through which this occurred by investigating how manipulations of sex steroids might affect this …

Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson

Department of Food Science and Technology: Faculty Publications

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcoholmicrobiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …

A Systems Genetics Approach To Drosophila Melanogaster Models Of Rare And Common Neurodevelopmental Disorders, Rebecca Macpherson

All Dissertations

Fetal Alcohol Spectrum Disorders are a group of disorders resulting from prenatal alcohol exposure, presenting with neurodevelopmental and facial abnormalities of varying severity. SSRIDDs and CdLS are rare disorders of chromatin modification, resulting in patients with a wide range of craniofacial, digit and/or neurodevelopmental abnormalities. All of these disorders have a wide range of clinical phenotypes and disease severity, yet the role of potential genetic modifiers and gene-gene or gene-environment interactions in disease pathogenesis is largely unknown and cannot be studied in humans. Insufficient numbers of patients with a single rare disorder prevent investigation of genetic factors beyond the focal …

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 …

The Relationship Between Cerebrovascular Impairment And Behavioral Abnormalities In Rats Exposed To Alcohol In Utero, Tiffany M. Knecht

Honors Thesis

Maternal consumption of alcohol during pregnancy can result in fetal alcohol spectrum disorders (FASD), which describes a range of developmental disorders. The goal of this study was to examine the association between impaired cerebrovascular function and behavioral abnormalities associated with FASD. We fed Sprague-Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy. We then performed short-term memory and motor coordination assessments on the offspring during adolescence or adulthood. Next, we examined cerebral arteriole reactivity to the vasodilators nitroglycerin, adenosine diphosphate, N-methyl-D-aspartate, and iloprost. We found impairment in eNOS-, nNOS-, and K-channel-dependent dilation …

Effects Of Acute And Repeated Alcohol Exposure On Expression Of Synaptic-Associated Genes In The Male And Female Mouse Mpfc, Dhruba Podder

Undergraduate Honors Theses

Alcohol use disorder (AUD) is a serious chronic brain disease; in 2021 there were ~29.5 million people in the U.S. diagnosed with AUD. Individuals with AUD often show cognitive impairment such as risky decision-making, difficulties with impulse control, and working memory deficits. This impairment is associated with structural and functional changes in the prefrontal cortex (PFC), an extensively interconnected region of the frontal lobe involved in executive control of goal-directed behaviors. Chronic alcohol exposure in rodents has been seen to cause deficits in performance in behavioral tasks which assess mPFC function such as working memory and behavioral flexibility. It is …

Moringa Oleifera Seed Water Extract Protects Alcohol-Induced Movement Disorder In Caenorhabditis Elegans, Ying Peng

Food and Machinery

It was investigated the alleviating effect of water-extracts from Moringa oleifera seeds (MWE) on alcohol damage, and explored the effects of Moringa seeds on the physiological changes of drunk nematodes. Different concentrations of MWE were used to interfere with nematodes drunkenness. Its movement, tissue ethanol concentration, calcineurin and acetylcholinesterase activity were evaluated. The results showed that the intervention concentration of MWE was 10 mg/mL, and the movement trajectory, frequency of head swinging and swallowing frequency of the nematode were significantly improved, compared with the control group. However, no significant difference was found compared to the un-treated group. MWE reduced the …

Higher Sexual Excitation Is Associated With An Increase In Sex-Linked Substance Use In Women With A History Of Unwanted Sexual Contact, Harper R. Jones, Tierney K. Lorenz

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Survivors of unwanted sexual contact have an increased likelihood of using substances in sexual situations, which puts them at heightened risk for intoxication-related harms. Separately, research has indicated that women may intentionally use substances in sexual situations to either enhance pleasure (i.e., increase sexual excitation) and/or reduce sexual anxiety or shame (i.e., reduce sexual inhibition), a phenomenon termed sex-linked substance use (SLSU). A predominant assumption in the literature is that women with unwanted sex histories are more likely to disengage during sex, suggesting greater inhibition-related SLSU; however, there is little prior research directly examining if women who have unwanted sex …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Effect Of Menstrual Cycle Phase On The Rewarding Properties Of Alcohol In Women, Annie K. Griffith

Theses and Dissertations--Psychology

Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse. One likely mechanism underlying this disparity is fluctuations of ovarian hormones, particularly estradiol (E2), across phases of the menstrual cycle. Pre-clinical and clinical studies have shown that higher E2 levels correlate with heavier patterns of alcohol consumption, suggesting E2 may modulate drinking. This relationship is thought to be mediated by the rewarding properties of alcohol. The present thesis tested the hypothesis that elevated E2 during the late follicular phase would increase the rewarding properties of alcohol. Fifty young-adult women participated in a within-subjects …

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 …

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 …

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. …

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 …

Hypocretin-Receptor Mrna Expression In The Central Amygdala Of Alcohol-Dependent And Non-Dependent Rats, Gabriel Aldridge

Electronic Theses and Dissertations

Hypocretin/Orexin (HCRT) neurotransmission facilitates drug-seeking behavior. HCRT neurotransmission at HCRT-receptors 1 and 2 (HCRT-R1 and -R2, respectively) is implicated in addiction. During the shift to alcohol-dependency, adaptations in neurotransmitter systems occur in reward- and stress-related brain regions. Specifically, neurotransmission systems in the central amygdala (CeA) are modulated by alcohol drinking/exposure. Therefore, this study investigated Hcrtr1 and Hcrtr2 mRNA expression in the CeA of alcohol-dependent rats and in non-dependent controls during acute alcohol withdrawal. Fos mRNA expression in the CeA of alcohol-dependent and non-dependent rats was also determined to assess adaptations in neuronal activation. To our knowledge, this is the first …

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar

School of Medicine Faculty Publications

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers …

Intramolecular Friedel-Crafts Addition Of Indoles To Tertiary Allylic Alcohols, Bryan H. Wakefield, Romie Barnes, Traeannah Brown, Ashley M. Jones, Victoria A. Knotts, Christina Martinetti

Journal of the South Carolina Academy of Science

An intermolecular Friedel-Crafts alkylation of indole and tertiary allylic alcohols has been developed. The allylic alcohols were synthesized using a two-step procedure, then exposure of these alcohols to diphenyl phosphate facilitated the desired annulation reaction. This reaction tolerated a variety of indole substitutions to yield 1H,2H,3H,4H-pyrido[1,2-a]indoles.

The Effect Of Ethanol On Cellular Movements And Development In C. Elegans, Caitlin N. O'Connor

West Chester University Master’s Theses

Neural tube development, which gives rise to the central nervous system, is vital to embryonic development. Neural tube defects, like spina bifida, are serious and common congenital defects which can result in life-long medical complications. Folic acid has been used as a preventative measure for neural tube defects and has appeared to decrease the occurrences of neural tube defects. However, the mechanism behind folic acid’s role in neural tube development is unclear. Furthermore, some evidence suggests that ethanol decreases the levels of folates and folate coenzymes in the fetal brain and downregulates folic acid metabolism genes. To better understand the …

Effects Of Catharanthine On Dopamine Release In The Nucleus Accumbens And Ethanol Consumption, Emily Baldwin

Undergraduate Honors Theses

This thesis discusses the history of catharanthine and related compounds, and their potential anti-addictive properties. Current research is exploring possible mechanisms of these properties. Past studies have found catharanthine has effects on neurons that project to the mesocorticolimbic system, an area implicated in addiction. We have seen that catharanthine decreases evoked dopamine (DA) release but increases basal DA release. This is the first study to investigate catharanthine’s effect on DA transmission in vivo. Using microdialysis, we determined the effect of catharanthine on DA in the nucleus accumbens of the striatum. This study determines the effect of different doses of …

Mechanisms Of Prenatal Ethanol Exposure On Causing Developmental Defects Associated With Fetal Alcohol Syndrome Disorders, Jordan M. Powell

The Cardinal Edge

No abstract provided.

The Effects Of Alcohol On The Developing Drosophila Nervous System, Erica E. Hassoun

The Cardinal Edge

Ethanol is the most common human teratogen, contributing to fetal alcohol syndrome (FAS) when effects are the most severe. Key effects of fetal alcohol syndrome are observed in the nervous system. The high prevalence of prenatal alcohol exposure necessitates novel treatment and prevention methods. However, ethical issues prevent researching humans in utero. For this reason, the fruit fly Drosophila melanogaster has emerged as a model organism for studying FAS. Because Drosophila is a small and non-placental organism, its environment can be easily controlled, allowing for specific doses and time periods of ethanol exposure to be studied. This review discusses findings …

Distress Tolerance As A Mechanism Linking Violence Exposure To Problematic Alcohol Use In Adolescence, Charlotte Heleniak, China R. Bolden, Connor J. Mccabe, Hilary K. Lambert, Maya L. Rosen, Kevin M. King, Kathryn C. Monahan, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Adolescents exposed to violence are at elevated risk of developing most forms of psychopathology, including depression, anxiety, and alcohol abuse. Prior research has identified emotional reactivity and difficulties with emotion regulation as core mechanisms linking violence exposure with psychopathology. Scant research has examined behavioral responses to distress as a mechanism in this association. This study examined the association of violence exposure with distress tolerance—the ability to persist in the face of distress—and whether lower distress tolerance linked violence exposure with subsequent increases in depression, anxiety, and alcohol abuse problems during adolescence. Data were collected prospectively in a sample of 287 …

Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas

Dissertations

Alcohol has long been considered an exacerbator of diseases, disorders, and injuries as well as many of the accompanying symptoms. As an alternative approach, this dissertation explores alcohol as a catalyst for two different human disease conditions, human immunodeficiency virus (HIV)-associated neuroinflammation and traumatic brain injury (TBI)-induced iron toxicity. In HIV-1 infection, this dissertation presents a novel anti-viral drug, called Drug-S, for a possible inhibition and treatment of HIV-1 disease progression.

The first aim explores the influence of alcohol with HIV-associated neuroinflammation on macrophage migration across an in vitro model of the blood brain barrier. There is a gap in …

Eeg Features Of Explore-Exploit Decision-Making In Alcohol Use Disorder, Ethan Campbell

Psychology ETDs

Little research has assessed explore-exploit behavior in addiction using drug cues and even fewer studies have measured the neural activity underlying these behaviors. The present study aims to explore brain mechanisms of disordered decision-making in alcohol use disorder (AUD) through electroencephalography (EEG) during performance of a novelty bandit task with alcohol imagery and using a validated computational model of explore-exploit dynamics. Individuals with AUD (n = 28) and age and sex-matched controls (n = 27) showed differences in choice behavior and showed differences in EEG activity as a function of exploratory behavior, chosen stimulus type, and explore-exploit computational …

Assessment Of Pathogenic Changes In The Gut-Liver Axis In Plwh With Heavy Alcohol Drinking And Gut Dysbiosis Marked By Decreased Butyrogenic Potential., Smita Ghare, Vaughn Bryant, Richa Singhal, Sabina Gautam, Chanakya Charan Tirumala, Andrea Reyes-Vega, Craig J. Mcclain, Ronald Cohen, Varand Govind, Robert L. Cook, Shirish Barve

Faculty Scholarship

Purpose: People living with HIV infection (PLWH) experience increasing risk for non-AIDS diseases including liver dysfunction and injury. Both HIV-infection and heavy alcohol drinking (HAD) are known to cause gut microbial dysbiosis and systemic inflammation that may potentially contribute to altered Gut-Liver axis. However, the specific pathogenic features associated with combinatorial harmful effects of alcohol and HIV infection on gut-liver interactions are not completely understood. This study evaluate the pathogenic changes in the Gut-Liver axis in PLWH with HAD.