Medicine and Health Sciences Commons^™

Cocaine Induced Qt Prolongation, Jian Garcia Cruz, Alberto Pena, Julio Perez Rodriguez, Diana Othon Martinez, Roy Kondapavuluru

Research Symposium

Introduction:The Q-T interval represents ventricular repolarization of the heart. Prolongation of this interval is called Long QT syndrome (LQTS) and can lead to deadly arrythmias such as Torsades de Pointes. (1) According to the AHA, a Q-T interval is prolonged when it is >450ms in males and >460ms in females. LQTS has different etiologies (not limited to, but including): idiopathic, congenital, electrolyte abnormalities, and drug-induced. (2) However, recreational drugs such as cocaine may often be overlooked by some. A study by Magnano et al. found that cocaine can increase a QTc interval by 23 points (+/- 25) (P

Case …

Case Report: Levamisole-Induced Vasculitis After Cocaine Ingestion, Dakota Bigham, Adam Kvinta

Research Colloquium

Background: Levamisole, a common anthelmintic, is estimated to be present in up to 70% of the cocaine found in the United States. The exact mechanism of interaction between Levimasole and cocaine use is unknown. One such complication of ingestion of Levimasole contaminated cocaine is Levimasole Vasculitis. Here we report a case of the clinical presentation of Levimasole Vasculitis, and the emphasis on proper and thorough history taking when arriving at a diagnosis.

Case Presentation: Our case begins with a 71-year-old male with a history of COPD, hyperthyroidism, and polysubstance abuse who presented to the hospital with weakness, neck stiffness, chest …

Bioenergetics And Neuroimaging Research: A Neuropathophysiological Linkage In The Setting Of Cocaine Use Amongst Persons With Hiv, Cory J. White, Karl Goodkin

School of Medicine Publications and Presentations

Despite innovations in antiretroviral therapy (ART) that have transformed HIV infection from an acute illness with high mortality risk into a chronic, largely manageable disease, the viral reservoir that persists in brain continues to pose a risk for neurocognitive impairment and other deleterious clinical outcomes. ART regimens can inhibit viral integration and suppress replication to nondetectable levels in plasma and cerebrospinal fluid (CSF) but do not eliminate viral reservoirs, including that in brain ^[1]. Moreover, HIV transcripts within CSF cells have been associated with brain injury despite suppressive ART ^[2]. Comorbid HIV and cocaine use exacerbates brain atrophy …

Assessing The Involvement Of Projections From The Prelimbic Prefrontal Cortex To The Paraventricular Nucleus Of The Thalamus In Cocaine Withdrawal-Induced Anxiety, Clinton Coelho

MUSC Theses and Dissertations

Withdrawal from cocaine induces an immediate and powerful negative affective state which is characterized by feelings of agitation and anxiety in humans and anxiety-like behaviors in rodents. It has been hypothesized that the anxiogenic effects associated with cocaine withdrawal play a major role in continued cocaine use and drive relapse to cocaine seeking. The prelimbic (PL) medial prefrontal cortex is not only involved in the processing and regulation of negative emotions such as anxiety but also mediates relapse to cocaine-seeking. Subcortical hubs of the reward system that receive projections from the PL neurons are known to be dysregulated during different …

Molecular Insights And Clinical Outcomes Of Drugs Of Abuse Adulteration: New Trends And New Psychoactive Substances, Annagiulia Di Trana, Diletta Berardinelli, Eva Montanari, Paolo Berretta, Giuseppe Basile, Marilyn A. Huestis, Francesco Paolo Busardò

Institute of Emerging Health Professions Faculty Papers

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer's profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations' websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according …

A Changing Epidemic And The Rise Of Opioid-Stimulant Co-Use, Saeed Ahmed, Zouina Sarfraz, Azza Sarfraz

Department of Paediatrics and Child Health

No abstract provided.

Neuronal Activity Within The Ventral Tegmental Area Is Correlated With Cocaine-Seeking Behavior In Male, But Not Female, Rats, Colton D. Spencer, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

The objective of this study was to begin to determine the neurobiological underpinnings of psychosocial stress-induced cocaine seeking. Social defeat stress, achieved using the well-established resident-intruder procedure, is an ecologically-valid psychosocial stressor in rodents that may more closely recapitulate those psychosocial experiences that elicit cocaine craving and relapse in human cocaine users. Our laboratory has developed a model of psychosocial stress-induced relapse in rats in which extinguished cocaine seeking is reinstated by re-exposure to a discrete cue that signals impending social defeat stress. We previously reported that an individual rat’s predilection towards the display of active coping behaviors during prior …

Crime Scene Investigation: Simulated Post-Mortem Lc-Ms/Ms Analysis Of Cocaine And Cocaine Metabolites In Synthetic Human Serum, Matt J. Vergne

Faculty Works

This laboratory experiment introduces upper-division undergraduate analytical chemistry students to liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a forensic application: the analysis of cocaine and metabolites of cocaine in simulated serum ostensibly from drug overdose victims. For this investigation, students developed the analytical methods. First, the students determined the multiple reaction monitoring (MRM) transitions and optimized collision energy. The MS methods developed were then added to an LC method for LC-MS/MS quantitation with a 2.5 min run time. Students successfully quantified the drugs and metabolites, and they were able to identify which samples indicated cocaine use and overdose

Caldag-Gefi Mediates Striatal Cholinergic Modulation Of Dendritic Excitability, Synaptic Plasticity And Psychomotor Behaviors., Jill R. Crittenden, Shenyu Zhai, Magdalena Sauvage, Takashi Kitsukawa, Eric Burguière, Morgane Thomsen, Hui Zhang, Cinzia Costa, Giuseppina Martella, Veronica Ghiglieri, Barbara Picconi, Karen A. Pescatore, Ellen M. Unterwald, Walker S. Jackson, David E. Housman, S. Barak Caine, David Sulzer, Paolo Calabresi, Anne C. Smith, D. James Surmeier, Ann M. Graybiel

Department of Neuroscience Faculty Papers

CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. …

Neuroactivational And Behavioral Correlates Of Psychosocial Stress-Induced Cocaine Seeking In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Stephany J. Mcdonald, Samantha De Guzman, Nicole E. Hubbard, Colin M. Kulick-Soper, Jessica J. Debski, Bianca Patel, Daniel Manvich

Rowan-Virtua Research Day

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models …

The Dopamine D3 Receptor Antagonist Vk4-40 Attenuates Morphine-Induced Hyperactivity But Not Cocaine-Induced Hyperactivity In Mice, Desta M. Pulley, Jessica J. Debski, Daniel Manvich

Rowan-Virtua Research Day

In light of the increasing rates of opioid abuse in the US, the search for viable medications to treat opioid abuse disorder (OUD) has become ever more urgent. Opioids exert their abuse-related effects in part by indirectly increasing dopamine (DA) neurotransmission in the mesolimbic system, a dopaminergic projection arising in the ventral tegmental area and terminating in the nucleus accumbens. The DA D3 receptor (D3R), which belongs to the D2 family of dopamine receptors (D2, D3 , D4 receptor subtypes), is highly expressed in these brain regions and has shown strong potential as a pharmacotherapeutic target for the treatment of …

Effects Of Cocaine And/Or Heroin Use On Resting Cardiovascular Function, Shabber Syed Bs, Lina A. Shkokani Bs, Leslie H. Lundahl Phd, Renato S. Roxas Md, Philip D. Levy Md, Mark K. Greenwald Phd

Medical Student Research Symposium

Background: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease (CVD), but confounded by other factors.

Objectives: We examined effects of chronic (years of regular use) and recent (past-month) use of cocaine and heroin, controlling for other factors, on resting cardiovascular function.

Methods: In a sample of cocaine and/or heroin users (N=292), we obtained data on demographics, body mass index (BMI), history of substance use, and electrocardiogram, heart rate (HR) and blood pressure (BP). Following bivariate correlations, three-block (1: demographics, BMI; 2: tobacco, alcohol, marijuana; 3: cocaine, heroin) regression analyses were …

Organic Cation Transporter 3 And The Dopamine Transporter Differentially Regulate Catecholamine Uptake In The Basolateral Amygdala And Nucleus Accumbens, Katherine M. Holleran, Jamie H. Rose, Steven C. Fordahl, Kelsey C. Benton, Kayla E. Rohr, Paul J. Gasser, Sara R. Jones

Biomedical Sciences Faculty Research and Publications

Regional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation. Previous work has shown that catecholamine clearance in the NAcc is largely mediated by the dopamine transporter (DAT), but clearance in the BLA is less DAT‐dependent. A growing body of literature suggests that organic cation transporter 3 (OCT3) also contributes to catecholamine clearance in …

Role Of Extracellular Vesicles In Substance Abuse And Hiv-Related Neurological Pathologies, Katherine E. Odegaard, Subhash Chand, Sydney Wheeler, Sneham Tiwari, Adrian Flores, Jordan Hernandez, Mason Savine, Austin Gowen, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and …

Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.

Engineered Extracellular Vesicles Loaded With Mir-124 Attenuate Cocaine-Mediated Activation Of Microglia, Ernest T. Chivero, Ke Liao, Fang Niu, Ashutosh Tripathi, Changhai Tian, Shilpa Buch, Guoku Hu

Journal Articles: Pharmacology & Experimental Neuroscience

MicroRNA-124 (miR-124), a brain-enriched microRNA, is known to regulate microglial quiescence. Psychostimulants such as cocaine have been shown to activate microglia by downregulating miR-124, leading, in turn, to neuroinflammation. We thus rationalized that restoring the levels of miR-124 could function as a potential therapeutic approach for cocaine-mediated neuroinflammation. Delivering miRNA based drugs in the brain that are effective and less invasive, however, remains a major challenge in the field. Herein we engineered extracellular vesicles (EVs) and loaded them with miR-124 for delivery in the brain. Approach involved co-transfection of mouse dendritic cells with Dicer siRNA and RVG-Lamp2b plasmid to deplete …

Gut Integrity, Microbial Translocation, Immune Activation, Inflammation And Vitamin D In Drug Users Living With Hiv, Jacqueline S. Hernandez

FIU Electronic Theses and Dissertations

The purpose of this study was to examine associations between MT, immune activation, inflammation, gut integrity and vitamin D status in the context of cocaine use among People Living with HIV (PLWH). One hundred cocaine and non-cocaine users living with HIV were selected from the Miami Adult Studies in HIV cohort. Blood samples were collected to assess MT (LPS), immune activation (sCD163 and sCD27), inflammation (IL-6, TNF-a, hs-CRP, IL-17 and IL-22), gut integrity damage (I-FABP) and vitamin D status. Data on socio-demographic characteristics, anthropometrics, diet and disease progression were collected. Descriptive statistics, independent t-test, multiple linear and logistic regressions were …

A Genome-Wide Association Study Of Cocaine Use Disorder Accounting For Phenotypic Heterogeneity And Gene–Environment Interaction, Jiangwen Sun, Henry R. Kranzler, Joel Gelernter, Jinbo Bi

Computer Science Faculty Publications

Background: Phenotypic heterogeneity and complicated gene-environment interplay in etiology are among the primary factors that hinder the identification of genetic variants associated with cocaine use disorder. Methods: To detect novel genetic variants associated with cocaine use disorder, we derived disease traits with reduced phenotypic heterogeneity using cluster analysis of a study sample (n = 9965). We then used these traits in genome-wide association tests, performed separately for 2070 African Americans and 1570 European Americans, using a new mixed model that accounted for the moderating effects of 5 childhood environmental factors. We used an independent sample (918 African Americans, 1382 European …

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing The Role Of Neuroinflammation And Brain Edema, Edward C. Mader Jr., Alexander B. Ramos, Roberto A. Cruz, Lionel A. Branch

School of Medicine Publications and Presentations

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild …

Astrocyte Sensitivity To Dopamine In Culture And Ex Vivo, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. This thesis illustrates effects of dopamine on cultured astrocytes and astrocytes in brain slices (ex vivo). In striatal cultures, extracellular dopamine triggered changes in astrocytic Ca²⁺ signaling and rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation, but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. To isolate possible mechanisms underlying these structural and functional changes, whole-genome RNA sequencing was …

Medications Development For Drug Addiction And Other Neuropsychiatric Disorders, Ariful Islam

Theses and Dissertations

Drug addiction and abuse especially opiate and psychostimulant abuse is a national and global crisis. IBNtxA (3-iodobenzoyl naltrexamine) is a novel mu opioid receptor (MOR) agonist, a naloxone derivative, structurally related to the classical MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, producing a unique pharmacological profile resulting in potent analgesia with reduced side effects. It has been found that M. vaccae has immunoregulatory effects that can prevent stress-induced exaggeration of neuroinflammation in the brain. The purpose of our pilot study is to develop medication for addiction and neuropsychiatric disorders. According to our purpose, …

Illicit Substance Use Effects On Burn Related Reconstruction Patient Outcomes And Complications Following Hospital Admission: Systematic Review And Meta-Analysis, Kevin Klifto, Pragna N. Shetty, Benjamin R. Slavin, Caresse F. Gurno, Stella M. Seal, Mohammed Asif, Scott Hultman

Research Day

Patients suffering from burn-related injuries admitted to the hospital concurrent illicit substance use are believed to be at an increased risk of poor outcomes and the development of complications following burn reconstruction, however data varies within the literature and remains controversial. This systematic review and meta-analysis compared outcomes and complications from studies during the years 1986 to 2017 between 15653 burn patients admitted to the hospital with substance use alcohol use reported by a positive toxicology screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, codeine/morphine, PCP, LSD, inhalants, solvents, aerosols, legal highs), or the patient on hospital admission to 299543 burn …

Substance Use Disorder Treatment Decision Aid For Adults In Chittenden County Vermont, Elizabeth V. Mcleod

Family Medicine Clerkship Student Projects

Substance Abuse Disorders (SUDs) are a prevalent public health concern in both the national and local arena resulting in millions of dollars in pubic health costs and loss of life. Navigating the treatment options available in Chittenden County can be time consuming, difficult, and delay treatment. In order to help guide adult patients and their families in Chittenden County along their journey towards recovery from SUDs, a treatment decision aid was developed for choosing the right level of care.

Discovery Of Novel Pharmacotherapeutics For Substance Use Disorders, Na-Ra Lee

Theses and Dissertations--Pharmacy

Substance use disorders are serious health concerns in the United States. Furthermore, the National Survey on Drug Use and Health reports a continuous increase in substance use disorders in the United States during the last 10 years. However, there are not many effective pharmacotherapeutics available for substance use disorders. The current dissertation is focused on research aimed at discovering pharmacotherapeutics for substance use disorders. First part of dissertation focused on discovering methamphetamine (METH) use disorder therapeutics targeting specific mechanism of METH action on dopaminergic neurons. The second part of dissertation focused on opioids and cocaine use disorder therapeutics targeting rewarding …

Measuring Glutamate And Oxygen In Brain Reward Circuits In Animal Models Of Cocaine Abuse And Decision-Making, Seth Richard Batten

Theses and Dissertations--Psychology

Drug-specific reward and associated effects on neural signaling are often studied between subjects, where one group self-administers drug and a separate group self-administers a natural reinforcer. However, exposure to drugs of abuse can cause long-term neural adaptations that can affect how an organism responds to drug reward, natural reward, and their reward-associated stimuli. Thus, to isolate drug-specific effects it is important to use models that expose the same organism to all of the aforementioned. Multiple schedules provide a means of dissociating the rewarding effects of a drug from the rewarding effects of food within a single animal. Further, drug users …

Endogenous Dopamine And Endocannabinoid Signaling Mediate Cocaine-Induced Reversal Of Ampar Synaptic Potentiation In The Nucleus Accumbens Shell, Anna E. Ingebretson, Matthew C. Hearing, Ethan D. Huffington, Mark J. Thomas

Biomedical Sciences Faculty Research and Publications

Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During a 10–14 day period of abstinence from cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability. Re-exposure to cocaine during abstinence, however, rapidly reverses and depotentiates enhanced AMPAR signaling. To understand how re-exposure to cocaine alters AMPAR synaptic transmission, we investigated the roles of dopamine …

The Role Of Human Dopamine Transporter In Neuroaids, Jun Zhu, Subramaniam Ananthan, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation …

Modified Single Prolonged Stress Reduces Cocaine Self-Administration During Acquisition Regardless Of Rearing Environment, Rebecca S. Hofford, Mark A. Prendergast, Michael T. Bardo

Psychology Faculty Publications

Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in …

Regulator Of G Protein Signaling-12 Modulates The Dopamine Transporter In Ventral Striatum And Locomotor Responses To Psychostimulants, Joshua D. Gross, Shane W. Kaski, Adam B. Schroer, Kimberley A. Wix, David P. Siderovski, Vincent Setola

Clinical and Translational Science Institute

Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of …

The Effect Of Early Life Photoperiod Manipulation On Cocaine-Induced Behavioral Sensitization In Male And Female Japanese Quail, Shannon Elizabeth Eaton

Theses and Dissertations--Psychology

Estrogens seem to play a role in the locomotor activating effects of cocaine. Japanese quail provide a good model for hormonal manipulation as alterations of their photoperiod controls hormone levels. The current study aims to examine the role of early life photoperiod manipulation in cocaine-induced behavioral sensitization in quail. It was expected that if quail were raised on a short photoperiod, they would have a reduction in gonadal hormones and this reduction in hormones would affect the acquisition of cocaine-induced behavioral sensitization. Quail were raised on an 8L:16D or a 16L:8D light cycle. Following 2 days of habituation, quail were …