Animal Experimentation and Research Commons^™

Effects Of Novel Dopamine D4 Receptor-Targeted Compounds On Locomotor Activity And Anxiety-Like Behavior In Male And Female Sprague Dawley Rats, Samantha Alyse Walkow, Noah A. Ivak, Daniel Chandler, John Tkaczynski, Thomas M. Keck, Comfort A. Boateng, Eleni Papadopoulos, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was …

Assessing Sleep Quality In A Preclinical Model Of Low Back Pain Through Novel Noninvasive Methods, Lydia C. Saltz

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain (LBP) has widespread negative impacts on quality of life. Current treatments for chronic LBP fail to provide long-term efficacy and motivate the need to understand key drivers of poor patient outcomes. Mounting evidence indicates that sleep disturbances and chronic LBP have a strong reciprocal relationship. Women may be particularly vulnerable to the negative impacts of the sleep-pain axis, exhibiting greater prevalence in both conditions. However, the relationship between sleep, pain, and sex remains understudied. Preclinical models can be used to parse out characteristic sleep features that degrade with pain, which can be further broken out by …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Passive Integrated Transponders: An Effective Marking Technique For Individual Identification Of Anaxyrus Fowleri?, Emily Leprell

Honors College Theses

With the rise of fungal disease such as Chytridiomycosis, known as chytrid, causing massive population declines for many species of frogs and toads (order Anura), specific conservation strategies are needed now more than ever. In many cases, being able to mark and identify individuals is a necessary step in developing an effective conservation plan. Individual identification allows researchers to obtain accurate population estimates, which are needed to test the progress and validity of conservation management decisions. However, due to their unique life history, including cutaneous respiration and a dichotomous lifestyle, anurans are among the most difficult wildlife species to …

Designing An Optimal Thermal Preference Arena For Southern Cricket Frog (Acris Gryllus) Juveniles, Eleanor E. Briggs, David M. Phillips Jr.

Honors Theses

Climate change has been altering ecosystems across the world at a substantial rate, disrupting the delicate ecophysiological relationships between ecosystems and the organisms that live in them. Ectotherms, such as amphibians, rely on external temperatures to behaviorally thermoregulate, making it especially imperative to study their thermal biology. Thermal preference, which assesses the environmental temperature an organism would seek out in the absence of external stimuli, provides valuable information about an amphibian’s thermal biology and can be used to predict the effects of climate change on a species or population. A commonly used method to measure thermal preference is an arena …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …

Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.

Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.

Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory …

Exploring The Therapeutic Potential Of Trigonella Foenum-Graecum Extract-Loaded Transferosomal Gel In Freund's Complete Adjuvant-Induced Rat Models., Vandana Singh Ms., Hema Arya Ms., Bhavana Singh Dr., Koushal Dhamija Mr., Preeti Singh Dr., Gautam Kumar Dr.

Chulalongkorn Medical Journal

Abstract:

Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by inflammation and joint damage.

Objective: This study aimed to evaluate the antiarthritic activity of Trigonella foenum-graecum (TFG) Transferosomal gel in a Freund’s adjuvant-induced arthritic rat model and compare it with Diclofenac gel, a standard anti-inflammatory drug.

Methods: Arthritis was induced in rats by injecting a 0.1 mL (1mg/ml) CFA suspension into the left hind foot in the subplantar region, allowing them to develop arthritis for 21 days.

Results: Arthritis induction led to a significant increase in paw volume, indicative of inflammation. Treatment with both TFG-transferosomal gel and Diclofenac …

External Jugular Vein Catheterization Technique For Continuous Blood Sampling In Gilts, Preechaphon Taechamaeteekul, Yosua Kristian Adi, Chutikan Srisang, Pirada Virankabutra, Natchanon Dumniem, Jinda Singlor, Padet Tummaruk

The Thai Journal of Veterinary Medicine

External jugular vein blood collection is common in gilts and sows, but continuous sampling for hormonal and pharmacokinetic research requires catheterization. The standard protocol has remained largely unchanged for nearly 40 years. This study aimed to develop a modified external jugular vein catheterization technique in gilts. Ten gilts (72.0 ± 3.4 kg) underwent surgery under general anesthesia after 12-hour fasting. Sedation was induced with intramuscular Xylazine (4.4 mg/kg) and Tiletamine–Zolazepam (2.2 mg/kg), followed by intravenous Thiopental sodium (10 mg/kg). Once anesthetized, gilts were placed in dorsal recumbency, and the external jugular fossa was prepared under sterile conditions. A 10 cm …

Impact Of Acute Stress On Circadian Rhythm Regulation Of Locomotor Activity In Syrian Hamsters, Raquel A. Villarreal, Laura E. Garcia, Mario Gil

Research Symposium

Background: Disruptions of circadian rhythms, caused by factors such as environmental changes or stress, are linked to health conditions, including metabolic disorders, cardiovascular diseases, and mood disorders. Circadian rhythm disturbances are particularly relevant for understanding the etiology of conditions like insomnia, depression, and anxiety. The circadian rhythm, primarily regulated by the suprachiasmatic nuclei (SCN) in the hypothalamus, coordinates biological processes to align with daily environmental cycles. Acute stress, especially when experienced immediately upon waking, has been shown to disrupt these rhythms, impair sleep regulation, and exacerbate mood dysregulation. Given the significant clinical implications, understanding how stress impacts circadian rhythms is …

The Role Of The Female Reproductive Cycle In Social Communication And Relevance To Mental Health, Julissa Amaro Castillo, Fernando Dominguez, Ariana Hinojosa, Giselle Padilla, Mario Gil

Research Symposium

The female reproductive cycle is characterized by fluctuating hormones, including estrogens and progesterone, that are involved in reproductive health; however, they have also been linked to disorders like Premenstrual syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), mood swings, depression and others. The goal of this study is to use the Syrian hamster (Mesocricetus auratus) as an animal model to examine the influence of the reproductive cycle and hormones on behavior. Scent-marking activity known as flank marking is exhibited by territorial or sociable animals. In essence, animals mark their territory or convey information such as reproductive status by rubbing their flanks or …

Effects Of Arginine-Vasopressin In The Brain On Cardiovascular Function In A Psychosocial Stress Animal Model, Esmeralda Lopez-Garcia, Ariana V. Hinojosa, Esperanza I. Alaniz, Fernando Dominguez, Giselle Padilla, Mario Gil

Research Symposium

Background: Psychosocial stress impacts cardiovascular health, increasing the risk of events like myocardial infarction (MI), stress cardiomyopathy, and neuropsychiatric disorders, including Major Depressive Disorder (MDD) and Anxiety. However, our understanding of the biological mechanisms that connect psychosocial stress with negative cardiovascular and psychological outcomes remains incomplete. Arginine-vasopressin (AVP) is linked to both mental and physical health by regulating social behavior, blood pressure, and anxiety-related behaviors. This study investigates the potential cardioprotective effects of the neuropeptide AVP, in an effort to generate evidence that it may strengthen heart function and lessen the severity of adverse cardiovascular events caused by stress, brain …

Investigating The Relationship Among Environmental Factors, Reproductive Status, And Stress In A Preclinical Model Of Endocrine Function In Women’S Translational Health, Bianca A. Camacho, Laura Emma Garcia, Raquel Villarreal, Mario Gil

Research Symposium

Background: The average menstrual cycle of a healthy adult woman is a duration of approximately 28 days, during which in the follicular phase (first 14 days) the progesterone hormone is at a stable level while estrogen increases to its peak level on day 14. Day 14 is known as ovulation, during which progesterone increases during its Luteinizing Hormone (LH) surge while estrogen decreases. Menses, known colloquially as a woman’s “period,” begins approximately at day 14 after ovulation and lasts an average of 7 days. The luteal phase, otherwise known as the secretory phase, lasts for the remaining 14 days until …

Exploring The Effects Of Serotonin And Ssris On The Neurological, Behavioral, And Cardiovascular Systems Under Induced Stress –Using The Animal Model Of The Syrian Hamster, Ariana V. Hinojosa, Esperanza I. Alaniz, Esmeralda Lopez-Garcia, Giselle Padilla, Fernando Dominquez, Mario Gil

Research Symposium

Background: Serotonin is a neurotransmitter that has been found to have a wide range of effects on not just the neuropsychological processes but has also been found to exert effects outside the central nervous system (CNS); regulating numerous biological processes, such as metabolism, gastrointestinal system, reproductive function, and even the cardiovascular system. However, there is still a limited understanding of how serotonin affects all these systems due to its complexity and ability to regulate homeostasis. This project aims to create a stronger foundation of knowledge about serotonin and its influence on the interaction between the CNS, behavior, and cardiac function …

Antibiotic Resistome, Mobile Genetic Elements, And Virulence Profile Of Multidrug-Resistant Enterobacteriaceae Isolated From Healthy Philippine Native Chicken As Revealed By Analysis Of Whole Genome Sequence, Alvin P. Jimenez, Grignard James R. Buday, Rina B. Opulencia

The Philippine Agricultural Scientist

Gram-negative bacteria, particularly Enterobacteriaceae, acquire antibiotic resistance via horizontal transmission of resistance genes in poultry farms that give rise to multidrug-resistant (MDR) strains. The presence of MDR strains that are potentially pathogenic and zoonotic poses a concern to animal and human health. The aims of this study were to isolate MDR, potentially pathogenic Enterobacteriaceae from Philippine native chicken (PNC) and to analyze the genome of a representative MDR isolate to gain insights into the mechanisms, acquisition, and transmissibility of antibiotic resistance genes (ARGs). Cloacal swabs from PNC were used to isolate putative Salmonella that were then tested for antimicrobial …

Contraceptive Hormone Influences On The Role Of Primary Reinforcement And Reinforcer-Enhancement In Nicotine Self-Administration, Kathleen Robin Mcnealy

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Hormonal contraceptives contain a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a synthetic progestin (e.g., levonorgestrel/LEVO) and can exacerbate nicotine intake. However, whether altered intake reflects changes in nicotine reinforcement or enhancement by nicotine of co-occurring reinforcers is unknown. This reinforcer-enhancement effect is evidenced in rats when nicotine self-administration is increased by the presence of a visual stimulus (VS) reinforcer. This dissertation examined the effects of EE and LEVO on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and assigned to receive daily injections of EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; …