Behavioral Neurobiology Commons^™

Influences Of Sex, Alcohol, And Stress On Conditioned Fear Responses, Heyam K. Mayberry

MUSC Theses and Dissertations

Learned fear responses are acquired through the identification and association of threatening stimuli with aversive outcomes. Fear responding and the proper maintenance of defensive behaviors is integral to survival. However, without the homeostasis of such systems, fear responses can become maladaptive and lead to dysregulated behavioral responding. Psychological conditions such as alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often lead to impairments in fear learning, deficits in fear memory, and heightened fear responses. While there are clear sex differences in the prevalence of both AUD and PTSD, development of either disorder increases the risk for comorbid AUD/PTSD, leading …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Simulated Slot Machine Gambling In Relation To Sign-Tracking, Polina Krom

Graduate Theses, Dissertations, and Problem Reports (ETD)

The propensity to attribute incentive salience to reward-related cues, or sign-tracking (ST) has been linked to addiction in animal models and some initial human data. The current study explores the role of sign-tracking (ST), as a potential risk factor for problematic slot machine gambling, which abundantly features audiovisual reward-related cues, henceforth sensory features. A sample of healthy participants without gambling problems (n = 30) completed a Pavlovian-to-Instrumental Transfer (PIT) paradigm to assess ST propensity and played on a realistic slot machine simulator consisting of two versions: with sensory features (SF+) and without (SF-). Each game version had fixed bet sizes, …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Role Of Nucleus Accumbens Dopamine Receptor Signaling In The Suppression Of Punished Reward Seeking, Grace M. Joyner, Anna Caroline Toburen

Senior Theses

Previous studies have shown that within the nucleus accumbens (NAc), a brain region associated with motivation and reinforcement learning, activity of neurons expressing the dopamine D2 receptor (D2R neurons) act as a “break” on risky behavior associated with negative outcomes. Moreover, when these neurons are stimulated, rats were found to become more risk averse. However, the impact of dopamine signaling through NAc D2R neurons in risk avoidance is still unclear. To further explore the role of NAc dopamine signaling in punished reward-seeking, we tested rats in a novel punished food-seeking paradigm in which subjects are trained to choose between a …

Dendritic Spine Density And Morphology In The Dorsolateral Striatum Following A High Fat Diet, Tikva Nabatian

Dissertations, Theses, and Capstone Projects

Obesity rates have been dramatically rising in recent years and in 2017-2018 more than 42% of adults in the United States were obese. Obesity is associated with numerous health problems, including cardiovascular disease, stroke, insulin resistance, and type II diabetes. The prevalence of highly palatable and calorically dense foods high in fats and sugars is a significant factor in the increase in obesity rates. Many suggest that palatable food affects the brain in ways similar to drugs of abuse, reinforcing the consumption of highly palatable foods in the same way drugs reinforce drug use. While numerous weight loss programs and …

Cue Reactivity In Electronic Cigarette Users With Sign-Tracking Or Goal-Tracking Behaviors, Polina Krom

Graduate Theses, Dissertations, and Problem Reports (ETD)

Polina Krom

Cue reactivity is an important predictor of addiction course and relapse. However, cue reactivity is only observed after an addiction develops. As such, it is unclear to what degree cue reactivity represents a state stemming from the addiction process versus a trait-like propensity towards developing cue-reward associations. Work in animal models has pointed to important individual differences in trait-like inclination to attribute incentive salience to reward-predictive cues that is associated with addiction-relevant behavioral and neurobiological features. These individual differences manifest as sign-tracking (ST) and goal-tracking (GT) behaviors during Pavlovian conditioning. Little research has attempted to translate ST and …

Dietary Regulation Of Silent Synapses In The Dorsolateral Striatum, Allison M. Meyers

Dissertations, Theses, and Capstone Projects

Obesity and drugs of abuse share overlapping neural circuits and behaviors. Cravings for drugs of abuse increase during abstinence, a phenomenon known as incubation. In obesity, increased craving is observed in individuals during dieting. Diets often fail, with return to- or increase above- original weight. The extent to which this reflects an incubation phenomenon has not been carefully examined. One mechanism underlying incubation is the reemergence of a developmental mechanism called silent synapses. Silent synapses are 'temporary' synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. Drugs of abuse increase …

Sex Differences In Lateral Hypothalamic Extracellular Glucose Concentrations During Cumulative Dosing Of Methamphetamine In Rats, Joshua A. Jolton

Honors Program: Senior Projects (Public)

The present study experimentally investigated sex differences in lateral hypothalamic glucose concentrations following cumulative dosing of methamphetamine. Male (n=17) and female (n=11) rats were surgically implanted with enzyme-based glucose biosensors in the lateral hypothalamus. Rats then received a saline injection followed by four methamphetamine doses (0.025 mg/kg, 0.05 mg/kg, 0.1 mg/kg, and 0.2 mg/kg) spaced 55 minutes apart. We found that while there was a general decrease in glucose baseline throughout the study for both sexes, the magnitude of the decrease was significantly greater in females compared to males. On a rapid timescale, fixed sex effects existed at the lower …

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids …

Effects Of Repeated Intermittent Episodes Of Social Stress On The Acquisition And Extinction Of A Reward-Seeking Task, Nikki Sullivan

Honors Theses

Repeated exposure to stress is known to have a myriad of effects on the brain, contributing to the development of psychiatric disorders, such as anxiety, depression, and drug addiction. For example, rats undergoing repeated social stress develop increased cocaine self-administration. These effects of stress are not well-understood and are related to changes in the brain reward system. This study investigated the effects of repeated social stress on reward-seeking behavior via the acquisition and extinction of a discriminative stimulus (DS) task and on anxiety-like behavior in the elevated plus maze (EPM). Male rats underwent intermittent social defeat (4 sessions in 10 …

Overexpression Of Corticotropin-Releasing Factor In The Nucleus Accumbens Enhances The Reinforcing Effects Of Nicotine In Female Versus Male Rats., Uribe, Victor Correa, Briana Pinales, Rodolfo Flores, Bryan Cruz, Zhiyin Shan, Adriaan Bruijnzeel, Arshad Khan, Laura O'Dell

Departmental Papers (Biology)

This study assessed the role of stress systems in the nucleus accumbens (NAc) in promoting sex differences in the reinforcing effects of nicotine. Intravenous self-administration (IVSA) of various doses of nicotine was compared following overexpression of corticotropin-releasing factor (CRF) in the NAc of female and male rats. Ovariectomized (OVX) females were also included to assess the role of ovarian hormones in promoting nicotine reinforcement. Rats received intra-NAc administration of an adeno-associated vector that overexpressed CRF (AAV2/5-CRF) or green fluorescent protein (AAV2/5-GFP). All rats were then given extended access (23 h/day) to an inactive and an active lever that delivered nicotine. …

Addictions, Behavioral Addictions, And Pathological Internet Use As Internet Addiction - A Literature Review, Vy K. Nguyen

Publications and Research

Excessive and pathological uses of the Internet are observed and discussed often in our modern conversations. Access to the Internet has become so convenient that these behaviors can lead to consequences in many areas of our lives from social relationships to academic and professional work performance. A common term that people use to address this pattern of behaviors is “Internet Addiction” or more specific ones, such as “Social Media Addiction” or “Online Gaming Addiction.” However, in clinical psychology, addiction has its own specific definitions. It refers to a category and set of criteria that are distinguished from other mental disorders …

The Winding Road To Relapse: Forging A New Understanding Of Cue-Induced Reinstatement Models And Their Associated Neural Mechanisms, Mark D. Namba, Seven E. Tomek, M. Foster Olive, Joshua S. Beckmann, Cassandra D. Gipson

Psychology Faculty Publications

In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will …

The Effects Of Chronic Partial Sleep Deprivation And Chronic Voluntary Alcohol Consumption On Δfos B Accumulation, Kristian Ponder

Masters Theses, 2010-2019

The present study explores the relation between sleep restriction and alcohol use and the neural substrates that result from chronic behaviors. Accumulation of the transcription factors ΔFosB is suggested as a possible outcome of chronic behaviors, such as addiction. Sleep is discussed as possible mediating factor in the relationship between ΔFosB and chronic alcohol consumption. There were four experimental groups in this study: Control (C), Sleep Deprivation only (SD), Alcohol Exposure only (AO), and both sleep deprivation and alcohol exposure (B). Levels of ΔFosB accumulation in the Nucleus Accumbens (NAc) revealed a significant main effect of sleep deprivation, but no …

Drink Like A Lawyer: The Neuroscience Of Substance Use And Its Impact On Cognitive Wellness, Debra S. Austin

Sturm College of Law: Faculty Scholarship

Lawyers suffer from higher levels of anxiety and depression than the rest of the population, but most do not enter law school with these mental health issues. Disciplinary actions against attorneys involve substance abuse 50 to 75 percent of the time. However, neuroscience research has shown that both the brain and the genes enjoy the power of plasticity, which means that personal choices and environments shape the development of lawyers throughout their lives. Legal educators need a better understanding of what aspects or characteristics of legal education contribute to the decline in mental health of law students, lawyers, and judges, …

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …

Examining Oxytocin As A Potential Pharmacotherapy For Methamphetamine Addiction, Brittney M. Cox

MUSC Theses and Dissertations

Human and animal studies suggest that females differ in their motivation to use methamphetamine (meth), and have increased propensity to relapse. However, addiction pharmacotherapies have primarily only been tested in males, which may not accurately predict treatment outcomes in females. Evidence suggests that oxytocin, an endogenous peptide well known for its role in social behaviors and childbirth, is a promising addiction pharmacotherapy. This dissertation first examines sex differences in the effect of oxytocin to decrease meth and sucrose seeking. Our data indicate that systemic oxytocin decreased responding for meth differentially in males and females on a progressive ratio schedule of …

Sex-Specific Brain Deficits In Auditory Processing In An Animal Model Of Cocaine-Related Schizophrenic Disorders, Patricia A. Broderick, Taylor Rosenbaum

Publications and Research

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. …

The Effects Of Extended Access To Methamphetamine Self-Administration On Dopaminergic Markers In The Striatum, Joe Luevano

Open Access Theses & Dissertations

Methamphetamine (METH) abuse is a persistent problem in the U.S. and abroad. Escalation of METH use among independent users occurs for a variety of physiological and psychological reasons. Methamphetamine dependence may be attributed to the rewarding effect of this drug via the dopaminergic systems of the central nervous system (CNS). The presence of METH in the CNS increases synaptic release of dopamine. This increase in dopaminergic neurotransmission is thought to be directly attributed to the rewarding effects of METH. Following METH use, compensatory changes have been found to occur in the dopaminergic system during various periods of abstinence. It is …