Neuroscience and Neurobiology Commons^™

Examining The Neuronal Dopaminergic Pathway Underlying Sleep Behavior And Related Dopamine Sleep Disorders, Mary Beth Putz

Undergraduate Honors Theses

The human brain is an extremely complex organ with approximately 100 billion different neurons that are constantly sending and receiving messages. These messages are sent using the chemical messengers of the brain: neurotransmitters and neuromodulators. Mechanisms of neural control of sleep are substantially conserved across species. Evidence from multiple animal models including flies, zebrafish, and mice shows that the arousal, or wake phase, is regulated by conserved neuromodulators such as dopamine, norepinephrine, and serotonin. Since these neurotransmitter systems are distributed throughout the brain and sub-serve many functions in addition to sleep, the precise circuit mechanisms by which these neurotransmitters regulate …

Major Neurotransmitters In The Brain, Amy S. Yu '17

Independent Study

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review is …

Dopamine D1 Receptor Activity In The Basolateral Amygdala Is Important For Mediating Fear, Reward And Safety Discrimination Learning, Ka Ho Ng

Open Access Theses

Post traumatic stress disorder (PTSD) patients frequently show impairment in safety learning (Jovanovic, Kazama, Bachevalier, & Davis, 2012). Since the amygdala is known to be critical for emotional processing(Wassum & Izquierdo, 2015) and dopamine signaling in the amygdala is important for mediating both fear and reward learning, current experiments examined the role of dopamine signaling in the BLA in mediating both safety learning and reward seeking. We manipulated dopamine D1 receptor activity with a D1 receptor agonist (SKF 38393) or D1 receptor antagonist (SCH23390) either systemically or infused directly into the BLA 20 minutes prior to training rats in a …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …

Social Defeat Stress Induces Depression-Like Behavior And Alters Spine Morphology In The Hippocampus Of Adolescent Male C57bl/6 Mice, Sergio D. Iñiguez, Antonio Aubry, Lace M. Riggs, Jason B. Alipio, Roseanna M. Zanca, Francisco J. Flores-Ramirez, Mirella A. Hernandez, Steven J. Nieto, David Musheyev, Peter Serrano

Publications and Research

Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests. Hippocampi were then dissected and Western blots were conducted to quantify protein levels for …

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

The Effects Of Modafinil And Atomoxetine On Dopamine Signaling In The Striatal Subregions Of The Rat, Martin Bobak

Theses and Dissertations

In an effort to combat diseases and disorders that impede our health, comfort and well-being, an abundance of prescription drugs have emerged in the past 60 years. Many prescription drugs have remarkable efficacy for treating the primary symptoms of these diseases and disorders; however, some drugs carry negative side effects that impose their own adverse symptoms, albeit, often to a lesser degree than the primary symptoms. Thus, one of the main objectives of the pharmaceutical industry is to innovate and develop novel therapeutics, which remediate the primary symptoms of disease and lack undesirable negative side effects. However, in order to …

The Cognition-Enhancing Effects Of Psychostimulants Involve Direct Action In The Prefrontal Cortex, Robert C. Spencer, David M. Devilbiss, Craig Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. …

Dopamine Regulation Of Disengagement In The Basal Ganglia Circuitry, Mabel N. Terminel

Open Access Theses & Dissertations

Evidence suggests that dopamine (DA) is crucial for initiation and termination as well as sustained execution of movement. For the present study, it was hypothesized that DA plays a more important role in initiation and termination of movement than in its sustained production. To test these hypotheses, rats were trained to walk on a treadmill in a continuous and discontinuous (walk 30 secs/stop 15 seconds) fashion for one hour while striatal DA samples were collected using In Vivo Microdialysis (IVMCD). We predicted larger increases during discontinuous compared to continuous walking. It was found that brain dialysate levels of DA consistently …

Electrical Stimulation Uses Sodium Channel Dependent Depolarization To Produce Exocytotic-Like Dopamine Release And Rotational Behavior In Vivo, Alice Elaine Hernandez

Open Access Theses & Dissertations

The goal of this project was to establish Electrical Stimulation (ES) in combination with In Vivo Intracerebral Microdialysis (IVMCD) as a methodology to evoke exocytotic-like dopamine (DA) release. To provide evidence that ES mimics action potential-mediated DA exocytosis, we hypothesized that ES produces depolarization of the membrane potential that is dependent upon sodium (Na+) -channels to produce DA release concomitantly with rotational behavior. To test this, rats received electrode and cannulae implants along the medial forebrain bundle, which contains the DAergic nigrostriatal pathway, and a microdialysis probe at the striatum to undergo IVMCD testing. To begin, steady baseline DA levels …

Roles Of Dopamine D1 And D2, Opioid And Glutamate Nmda Receptor Signaling In The Acquisition And Expression Of Fat- And Glucose-Conditioned Flavor Preferences In Rats And C-Fos Analysis Of The Dopamine Mesotelencephalic And Nigrostriatal Pathways Following Intake Of Sugars And Fats In Rats, Julie Dela Cruz

Dissertations, Theses, and Capstone Projects

Systemic administration of the non-competitive NMDA antagonist, MK-801, demonstrated that acquisition, but not expression, were found to affect the orosensory-mediated (flavor/flavor: f/f) fructose-conditioned flavor preference (CFP). The present studies demonstrated a similar outcome when f/f and f/n processes were combined. Fat-CFP and glucose-CFP studies indicated that systemic injections of the NMDA antagonist, MK-801, were able to significantly reduce acquisition, but not expression, of Corn-Oil (CO)-CFP and glucose-CFP. Both studies appear to have mitigated effects on acquisition as compared to the separate orosensory and postingestive CFP studies.

Previous studies found that systemic administration of dopamine (DA) D1 (SCH23390) and D2 (raclopride) …

A Kinder, Gentler Dopamine. . . Highlighting Dopamine's Role In Behavioral Flexibility, Jeff A. Beeler, Roshan Cools, Monica Luciana, Sean B. Ostlund, Giselle Petzinger

Publications and Research

No abstract provided.

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

An Investigation Into The Presynaptic Actions By Which Amphetamine Activates Dopamine Signaling Within Striatal Subregions Of The Rat., Dan P. Covey

Theses and Dissertations

Despite decades of intense research and a consensus view in the field, the work presented herein provides strong evidence that the primary mechanism of amphetamine action should be re-evaluated. Rather than depleting vesicular dopamine stores and promoting non-exocytotic efflux through the dopamine transporter in vivo, recent evidence demonstrates that amphetamine augments phasic dopamine signaling instead. This signaling modality is critical for reinforcement learning and is dependent on intact vesicular stores. The new findings support over-activation of phasic dopamine signaling as a common mechanism in the addiction process.

Modulation Of Neuronal R-Type Ca2+ Channels (Cav2.3) By G Protein-Coupled Receptors, Lauren S. Page

Undergraduate Honors Capstone Projects

Neuronal R-type Ca²⁺ channels (Ca_v2.3) are expressed at high concentrations within the cortex, hippocampus and striatal regions of the brain, where they participate in neuronal excitability and synaptic signaling. This pattern of expression may signify a connection between Ca_v2.3 channel function and neurological disorders such as Parkinson's Disease (PD) and Huntington's Disease (HD). Both of these disorders are caused by inadequate secretion of the neurotransmitter dopamine within the striatum. The first step in characterizing the potential importance of Ca_v2.3 in PD and HD is to examine its modulation by G-protein-coupled dopamine receptors. Specifically, …

Medial Prefrontal Cortex Lesions Impair Decision-Making On A Rodent Gambling Task: Reversal By D1 Receptor Antagonist Administration, Tracie A. Paine, Samuel K. Asinof, Geoffrey W. Diehl, Anna Frackman, Joseph Leffler

Faculty & Staff Scholarship

Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using “gambling” tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered “advantageous” and lead to greater net rewards (food pellets) than the other 2 “disadvantageous” options. Once rats attained stable levels of performance on …

The Role Of Progesterone Receptor In The Development Of The Mesocortical Dopaminergic Pathway, Jari Willing

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical dopaminergic pathway, comprised of projections from the ventral tegmental area (VTA) to the prefrontal cortex (PFC), mediates many of the most complex forms of cognitive behaviors and has been associated with clinical disorders such as ADHD and schizophrenia. While this circuit continues to develop throughout much of the lifespan, there is a rapid period of maturation, early in development, in which this circuit is highly sensitive to disruption. Steroid hormone receptors are powerful transcription factors, capable of affecting a variety of neurodevelopmental processes and are expressed in many regions throughout the developing brain. Specifically, the nuclear progesterone receptor …

Cocaine-Induced Reinstatement Of A Conditioned Place Preference In Developing Rats: Involvement Of The D2 Receptor, Kimberly A. Badanich, Cheryl L. Kirstein

Psychology Faculty Publications

Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement …

Chronic Ethanol Exposure Causes Disinhibited Behavior In Drosophila, Estrella Padilla, Kyung-An Han

COURI Symposium Abstracts, Summer 2012

Ethanol consumption is frequently associated with disinhibited sexual and locomotor behaviors in humans. Dopamine, a major monoamine found in vertebrates and invertebrates, is implicated in these processes since it regulates motivation, reward, motor control, and sexual behaviors. The goal of this study is to elucidate the role of dopamine in ethanol-associated behavioral disinhibition using the genetically tractable model system Drosophila melanogaster. Previous studies have shown a requirement for normal dopamine neurotransmission for ethanol-induced courtship disinhibition. Furthermore, genetic manipulation of the dopamine system revealed that D1 receptor activity is important for disinhibition and D2 for sensitization. The current study focuses …

Ethanol Reward Conditioning In Drosophila Melanogaster, Isaac A. Moya^, Young-Cho Kim, Kyung-An Han*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Validation On Sodium Channel Dependence By Electrical Stimulation-Induced Dopamine Release, Alice E. Hernandez ^, Mabel N. Terminel, Edward Castaneda *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Dysregulation Of System Xc- And Its Impact On Cocaine Seeking, Aric Madayag

Dissertations (1934 -)

Abnormal glutamate signaling in the brain, particularly in the nucleus accumbens core, contributes to compulsive cocaine-seeking behavior. In the nucleus accumbens, two distinct pools of glutamate exist. The synaptic pool stimulates excitatory postsynaptic receptors, leading to cocaine seeking. Cystine-glutamate exchange by system xc- contributes to the extrasynaptic pool and regulates neurotransmission by activating extrasynaptic receptors including inhibitory Group II metabotropic glutamate receptors, positioning this as an important mechanism for regulating nucleus accumbens activity. We and others have found decreased levels of cystine-glutamate exchange in animals withdrawn from chronic cocaine administration. In chapter 1, we describe studies directly implicating diminished system …

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 …

Examination Of The Neurochemical Mechanisms That Mediate Nicotine Withdrawal In Adolescent And Adult Rats, Luis Alberto Natividad

Open Access Theses & Dissertations

Introduction: The mechanisms that mediate nicotine withdrawal are presently unclear and age group differences in the neurochemical effects of withdrawal have been largely unexplored. Previous studies in our laboratory demonstrated that adult rats display a decrease in extracellular levels of dopamine in the nucleus accumbens (NAcc) during nicotine withdrawal and this decrease is reduced in adolescent rats (Natividad et al., 2010). The goal of this dissertation was to examine whether these age group differences in dopamine during withdrawal are mediated via excitatory and inhibitory mechanisms that modulate dopamine in the cell body region of the ventral tegmental area (VTA). Methods: …

Maternal Separation Affects Dopamine Transporter Function In The Spontaneously Hypertensive Rat: An In Vivo Electrochemical Study, Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell

Neuroscience Faculty Publications

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR …

Role Of Dopamine In Impulse Control, Paul Rafael Sabandal ^, Young-Cho Kim, Kyung-An Han *

COURI Symposium Abstracts, Summer 2011

No abstract provided.

Dysfunctional Play And Dopamine Physiology In The Fischer 344 Rat, Stephen M. Siviy, Cynthia A. Crawford, Garnik Akopian, John P. Walsh

Psychology Faculty Publications

Juvenile Fischer 344 rats are known to be less playful than other inbred strains, although the neurobiological substrate(s) responsible for this phenotype is uncertain. In the present study, Fischer 344 rats were compared to the commonly used outbred Sprague-Dawley strain on several behavioral and physiological parameters in order to ascertain whether the lack of play may be related to compromised activity of brain dopamine (DA) systems. As expected, Fischer 344 rats were far less playful than Sprague-Dawley rats, with Fischer 344 rats less likely to initiate playful contacts with a playful partner and less likely to respond playfully to these …

Psychostimulants As Cognitive Enhancers: The Prefrontal Cortex, Catecholamines And Attention Deficit Hyperactivity Disorder, Craig Berridge, David M. Devilbiss

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention deficit hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically-relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally-activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses …

Dopamine’S Role In Ethanol Induced Behavioral Disinhibition, Erick Saldes^, Kyung-An Han*

COURI Symposium Abstracts, Spring 2011

Ethanol is commonly associated with disinhibited motor and sexual behaviors in humans. Dopamine and serotonin are implicated in these processes since they regulate reward, motivation, aggression, movement control, and sexual behavior. Disinhibited behavior such as impulsivity (loss of impulse control) is also related to addiction. The major goal of this study is to identify the role of dopamine in disinhibited behavior using the genetic model system, Drosophila melanogaster.  For this task we developed a novel apparatus called Flypub. It is a plastic chamber with a clear top for recording and monitoring fly behavior before, during, and after ethanol exposure. …