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Neurochemical Signaling Of Reward-Based Learning In Ventral Tegmental Area Dopamine Neurons, Kyla F. Wholley

Dissertations, Theses, and Capstone Projects

Ventral tegmental area (VTA) dopamine neurons signal and participate in reward-related learning. Specifically, dopamine is postulated to encode reward-related environmental stimuli to compute reward prediction errors (RPEs). It is through the computation and maintenance of RPEs that learning occurs. However, little is known about the neural mechanisms that underlie how dopamine neurons compute RPEs and facilitate reward-related learning. The present study utilized fiber photometry in conjunction with a Pavlovian reward-based task to identify how GABA inputs to VTA dopamine neurons contribute to the computation of RPEs and reward-based behavior. Activity of GABA inputs to VTA dopamine neurons increased for reward-predicting …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Quantifying Psychostimulant-Induced Sensitization Effects On Dopamine And Acetylcholine Release Across Different Timescales, Georg Lange

Dissertations, Theses, and Capstone Projects

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Contributions Of Reward Identity And Time Prediction Errors To Pavlovian Learning, Daniel B. Siegel

Dissertations, Theses, and Capstone Projects

Some models of associative learning attempt to explain effects such as blocking and unblocking as reflecting a prediction error (PE): Associative strength, and thereby learning, are said to be greater when the unconditioned stimulus (US) received following a cue deviates from one’s expectations. Some models of PE-motivated behavior and PE-relevant brain activity represent the US as a single quantitative variable for outcome value, and that learning therefore only occurs when outcome value differs from expectations. There is growing evidence to suggest that changes in other dimensions of reward, such as identity and timing, also contribute to learning. In Experiment 1, …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Synthesis And Evaluation Of C-10 Nitrogenated Aporphine Alkaloids At Serotonin And Dopamine Receptors, Anupam Karki

Dissertations, Theses, and Capstone Projects

Aporphine alkaloids, belonging to the isoquinoline class of compounds, have been investigated as a potential source of ligands for Central Nervous System (CNS) receptors. Previous research indicates that the aporphine scaffold may be manipulated to synthesize selective ligands for serotonin and dopamine receptors. Novel aporphine alkaloids containing C10 nitrogen substitutions were synthesized, and their affinities were evaluated at serotonin (5-HT1A, 5-HT1B, 5-HT2A, 5-HT7A) receptors and dopamine (D1, D2, D3, D4, and D5) receptors. Two series of racemic aporphine compounds with C10 nitrogenous functionalities were synthesized and analyzed at the aforementioned receptors. The first series of aporphine alkaloids contain C10 nitro, …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Murine Genetic Variance In Sugar And Fat-Conditioned Flavor Preferences: Roles Of Dopamine, Opioid And Nmda Receptors And Nutritive Sensing, Tamar T. Kraft

Dissertations, Theses, and Capstone Projects

As obesity and diabetes have emerged as a severe public health crisis, understanding the mechanisms underlying the consumption of sugars and fats has become a topic of vigorous study. From a biological standpoint, genetic dispositions, neurochemical and hormonal influences, and predetermined orosensory and postingestive signals that modulate the hunger and satiety process may govern physiological aspects of the obesity puzzle. In addition to an innate appetite and attraction for simple carbohydrates and fats, learning plays an important role in modulating preferences for sugar- and fat-rich foods in rodents, including inbred mouse strains. Marked genetic variance has been observed among murine …

Structure And Function Of Dopamine In The Inner Ear And Auditory Efferent System Of A Vocal Fish, Jonathan T. Perelmuter

Dissertations, Theses, and Capstone Projects

The neuromodulator dopamine is considered essential for coordinating the internal motivational state of an organism with appropriate behavioral responses to stimuli in the external environment. This could be accomplished by modifying the function of neural circuits involved in sensory processing such that they are “tuned in” and optimally sensitive to important stimuli during critical time windows. While dopamine modulation of auditory processing has been studied in the central nervous system, neuromodulation can also occur outside the brain, in the inner ear. The majority of investigations of dopamine in the ear are conducted using rodents and focus on its role in …

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …

The Nucleus Accumbens Core Dopamine D1 And Glutamate Ampa/Nmda Receptors Play A Transient Role In The Performance Of Pavlovian Approach Behavior, Veronica Dobrovitsky

Dissertations, Theses, and Capstone Projects

The role of the nucleus accumbens core (NAc core) continues to be redefined with newly acquired data on neurochemical mechanisms mediating the learning and performance of behavior. Previous empirical data showed that dopamine transmission at the D1 receptor (D1R) plays a transient role in the expression of learned Pavlovian approach behavior. Here we show that, prior to overtraining, dopamine activity at D1Rs specifically within the NAc core is critical for the performance of approach behavior elicited by the recently-acquired reward-paired cue. Blockade of D1Rs in the NAc core, but not the dorsomedial striatum or NAc shell, disrupted approach responses during …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

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) …