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Psychotropic Effects Of Cannabis Components On The Mesolimbic Dopaminergic System, Christopher Norris 2018 The University of Western Ontario

Psychotropic Effects Of Cannabis Components On The Mesolimbic Dopaminergic System, Christopher Norris

Electronic Thesis and Dissertation Repository

The two most abundant phytochemical compounds in cannabis are cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC). THC is the primary psychoactive component of cannabis and is a partial CB1 receptor (CB1R) agonist. THC is believed to be responsible for the motivational and dependence-producing effects of cannabis and causes psychotomimetic and affective processing disturbances. Conversely, CBD, is non-psychoactive, acts as a 5-HT1A receptor agonist, antagonizes CB1Rs, and possesses both anti-psychotic and anxiolytic properties. The neural substrate believed to be responsible for many of the effects of cannabis is the dopaminergic, mesolimbic reward pathway which is responsible ...


Neonatal Stimulation Of Pkc Epsilon Signaling Normalizes Fragile X-Associated Deficits In Pvn Oxytocin Expression And Later-Life Social And Anxiety Behavior, Alexandra E. Marsillo 2018 The Graduate Center, City University of New York

Neonatal Stimulation Of Pkc Epsilon Signaling Normalizes Fragile X-Associated Deficits In Pvn Oxytocin Expression And Later-Life Social And Anxiety Behavior, Alexandra E. Marsillo

All Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is an inherited developmental disorder characterized by disturbances in emotional and social behavior. Our studies have revealed suppressed hippocampal PKCε expression in Fmr1 knockout (KO) mice, the leading model of FXS. To compensate for this deficiency, we stimulated PKCε in neonatal KO mice by administering a selective PKCε activator, dicyclopropyl-linoleic acid (DCP-LA), and studied its effect on ventral hippocampal neurons and a proximal target of the ventral hippocampus, the hypothalamus, which regulates social and emotional behavior. We observed that at postnatal day 18 (P18), vehicle-treated KO mice displayed increased surface localization of the 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA ...


An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi 2018 University of Surrey, UK

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood ...


Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge 2018 Dartmouth College

Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge

Open Dartmouth: Faculty Open Access Scholarship

Serotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A) receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current), or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of ...


Transcription Factor Pebbled/Rreb1 Regulates Injury-Induced Axon Degeneration, Jonathan E. Farley, Thomas C. Burdett, Romina Barria, Lukas J. Neukomm, Kevin P. Kenna, John E. Landers, Marc R. Freeman 2018 University of Massachusetts Medical School

Transcription Factor Pebbled/Rreb1 Regulates Injury-Induced Axon Degeneration, Jonathan E. Farley, Thomas C. Burdett, Romina Barria, Lukas J. Neukomm, Kevin P. Kenna, John E. Landers, Marc R. Freeman

GSBS Student Publications

Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C2H2 zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in axon death. Loss of Peb in Drosophila glutamatergic sensory neurons results in either complete preservation of severed axons, or an axon death phenotype where axons fragment into large, continuous segments, rather than completely disintegrate. Peb is expressed in developing and mature sensory neurons, suggesting it is required to ...


Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin 2018 Virginia Commonwealth University

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On ...


Effort-Related Motivational Dysfunctions: Behavioral And Neurochemical Studies Of The Wistar-Kyoto Rat Model Of Depression, Brendan Abbott 2018 University of Massachusetts Amherst

Effort-Related Motivational Dysfunctions: Behavioral And Neurochemical Studies Of The Wistar-Kyoto Rat Model Of Depression, Brendan Abbott

Masters Theses

Depression and related disorders are characterized by motivational dysfunctions, including deficits in behavioral activation and exertion of effort. Animal models of relevance to depression represent a critical starting point in elucidating the neurobiological mechanisms underlying motivational dysfunctions. The present study explored the use of the Wistar-Kyoto (WKY) animal model of depression to examine effort-related functions as measured by voluntary wheel running and performance on a mixed fixed ratio 5/progressive ratio (FR5/PR) operant task. Given the known link between activational aspects of motivation and the mesocorticolimbic dopamine (DA) system, the behavioral effects of d-amphetamine (0.5 and 1.0 ...


Mapping A Pup-Responsive Pathway From The Medial Preoptic Area To The Ventral Tegmental Area., Matias Andina 2018 University of Massachusetts Amherst

Mapping A Pup-Responsive Pathway From The Medial Preoptic Area To The Ventral Tegmental Area., Matias Andina

Masters Theses

Maternal behavior is the complex array of caregiving behaviors females display towards offspring. In rats, the transition to motherhood depends on the action of various hormones, especially estradiol near parturition, which primes the maternal circuitry to respond to pups upon first encounter at parturition with appropriate maternal behavior. Although virgin rats avoid pups, new mothers are highly motivated to interact with pups, and their maternal behavior depends on the functional interaction between the medial preoptic area (mPOA) and the ventral tegmental area (VTA). However, a precise mapping of the VTA-projecting mPOA neurons remains to be elucidated. To determine whether pup-responsive ...


Prior Voluntary Wheel Running Prevents Memory Deficits And Enhanced Neuropathic Pain Presenting After Morphine Dosing Ceases, Nathan Plattner 2018 University of Colorado, Boulder

Prior Voluntary Wheel Running Prevents Memory Deficits And Enhanced Neuropathic Pain Presenting After Morphine Dosing Ceases, Nathan Plattner

Undergraduate Honors Theses

Clinical research studies show that chronic pain is a prevalent, difficult affliction to manage. The most common management for chronic pain is opioids, which research is showing to paradoxically induce persistent, worsened pain states as well as potentially having negative effects on memory. The necessity for understanding chronic pain and drug management options is apparent, and research is aiming to do just that. Exercise is one potential preventative measure or post hoc treatment possibility for chronic pain, as abundant research has shown. Knowledge of the interactions between exercise, morphine dosing, and peripheral nerve injury is nonexistent. As such, we desired ...


The Effects Of Increased Camp Levels On Neuronal Differentiation In Murine Embryonic Stem Cells, And The Creation Of A Crispr-Induced C.1252c>T Point Mutation In The Adcy5 Gene, Elizabeth Zepeda 2018 Humboldt State University

The Effects Of Increased Camp Levels On Neuronal Differentiation In Murine Embryonic Stem Cells, And The Creation Of A Crispr-Induced C.1252c>T Point Mutation In The Adcy5 Gene, Elizabeth Zepeda

Theses and projects

ADCY5-related dyskinesia is a rare movement disorder with early onset in childhood and adolescence. Previous studies linked this disease to various point mutations in the ADCY5 gene. Recent studies show that two of the point mutations cause an increase in cyclic adenosine monophosphate (cAMP) levels. However, it remains unknown how increased levels of cAMP result in the phenotypes associated with this disease. My study examines the effects of increased cAMP levels on neuronal differentiation of mouse embryonic stem cells (mESCs). My experiments demonstrated successful differentiation of mESCs into the dopaminergic neuronal lineage, indicated by the presence of Tuj 1 (a ...


Extracellular Adenosine Protects Microglia-Like Cells During Simulated Ischemia, Anya Kim 2018 University of Iowa

Extracellular Adenosine Protects Microglia-Like Cells During Simulated Ischemia, Anya Kim

Honors Theses at the University of Iowa

Microglia are the surveillant immune cells of the brain, and as such they help protect the nervous system by clearing pathogens and dead cells, producing neurotrophic factors, and maintaining homeostasis. As guardians of the brain, microglia may be especially important in neural repair following injuries such as ischemic stroke, a disease which takes 6.2 million lives worldwide every year. Although microglia respond to tissue injury after stroke, they are themselves also vulnerable to ischemic death. Protecting microglia from ischemia-induced cell death could promote brain tissue restoration after stroke. Given the well-known anti-inflammatory and protective effects of adenosine (Ado) on ...


Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy 2018 Virginia Commonwealth University

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations ...


Molecular Brain Adaptations To Ethanol: Role Of Glycogen Synthase Kinase-3 Beta In The Transition To Excessive Consumption, Andrew D. van der Vaart 2018 Virginia Commonwealth University

Molecular Brain Adaptations To Ethanol: Role Of Glycogen Synthase Kinase-3 Beta In The Transition To Excessive Consumption, Andrew D. Van Der Vaart

Theses and Dissertations

Alcoholism is a complex neuropsychiatric disease that is characterized by compulsive alcohol use and intensifying cravings and withdrawals, often culminating in physiologic dependency. Fundamental alterations in brain chemistry underlie the transition from initial ethanol exposure to repetitive excessive use. Key mediators of this adaptation include changes in gene expression and signal transduction. Here we investigated gene expression pathways in prefrontal cortex and nucleus accumbens following acute or chronic ethanol treatment, to identify genes with potentially conserved involvement in the long-term response of the corticolimbic system to repeated ethanol exposure. We investigated Gsk3b, which encodes glycogen synthase kinase 3-beta, as a ...


Transcriptional Characterization Of Neuronal Cell Populations In Prairie Voles, Conor J. Kelly 2018 University of Colorado Boulder

Transcriptional Characterization Of Neuronal Cell Populations In Prairie Voles, Conor J. Kelly

Undergraduate Honors Theses

As humans, we experience the profound biological necessity to form social bonds from the moment of birth. These bonds are imperative for normal development and impact our health and well-being, with strong social networks acting as a primary predictor of longevity. The lack of or disruption of such bonds can be debilitating, as shown by increased rates of mental and physical illnesses. Our understanding of social bonds has been limited because commonly used laboratory model organisms, such as rats and mice, do not form partner-specific social bonds. To study complex social behaviors, the monogamous rodent, the prairie vole (M. ochrogaster ...


Acute Stress-Induced Modulation Of Per1 Mrna Expression Through Cort-Dependent And Cort-Independent Mechanisms In Male Sprague-Dawley Rats, Alice Droeger 2018 University of Colorado, Boulder

Acute Stress-Induced Modulation Of Per1 Mrna Expression Through Cort-Dependent And Cort-Independent Mechanisms In Male Sprague-Dawley Rats, Alice Droeger

Undergraduate Honors Theses

Circadian disruption is a widespread symptom among stress-related mental disorders which indicates an influential relationship between two factors: circadian rhythms and stress. Circadian rhythms throughout the body depend on the suprachiasmatic nucleus (SCN) of the hypothalamus for alignment. The SCN uses an adrenal glucocorticoid hormone, corticosterone (in most rodents; CORT) as a communication device which aligns the peripheral clocks. CORT secretion is controlled by the hypothalamic-pituitary-adrenal (HPA) axis, and displays a daily basal rhythm as well as increases during acute stress. CORT is able to affect the molecular clock through the glucocorticoid response element (GRE). The current experiments examine whether ...


Nicotine Administration And Withdrawal And Its Effect On Sleep Latency, Relevant Sleep Variables, And Endogenous Corticosterone Levels In Mice, Vishnu Iyer 2018 University of Colorado, Boulder

Nicotine Administration And Withdrawal And Its Effect On Sleep Latency, Relevant Sleep Variables, And Endogenous Corticosterone Levels In Mice, Vishnu Iyer

Undergraduate Honors Theses

NREM and REM sleep have shown an exceptional importance in controlling various cognitive functions (Brown et al, 2012), and disruption of such sleep states can cause mental and physical impairments (Christie et al, 2008). Disruptions in sleep stages (Wakefulness, REM, NREM) can be identified via EEG recordings in mice without much interference (Mckenna et al, 2008). Circadian Rhythm, hormonal markers, and stress all affect the duration, intensity and timing of these sleep stages (Brown et al, 2004; Veasey et al 2004; Christie et al, 2008). One cohort of mice (n=7) underwent a baseline condition (BL), a nicotine administration condition ...


Alterations In Gabaergic Nts Neuron Function In Association With Tle And Sudep, Isabel Diane Derera 2018 University of Kentucky

Alterations In Gabaergic Nts Neuron Function In Association With Tle And Sudep, Isabel Diane Derera

Theses and Dissertations--Physiology

Epilepsy is a neurological disorder that is characterized by aberrant electrical activity in the brain resulting in at least two unprovoked seizures over a period longer than 24 hours. Approximately 60% of individuals with epilepsy are diagnosed with temporal lobe epilepsy (TLE) and about one third of those individuals do not respond well to anti-seizure medications. This places those individuals at high risk for sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as when an individual with epilepsy, who is otherwise healthy, dies suddenly and unexpectedly for unknown reasons. SUDEP is one of the leading causes of death in ...


Validating The Use Of Dreadds In The Study Of The Paraventricular Thalamus (Pvt) And Its Role As In Interface Of Circadian Information, Luke Millisor 2018 University of Colorado, Boulder

Validating The Use Of Dreadds In The Study Of The Paraventricular Thalamus (Pvt) And Its Role As In Interface Of Circadian Information, Luke Millisor

Undergraduate Honors Theses

How the brain and body coordinate the phase of their internal clocks has remained elusive despite years of study. The discovery of clock genes showed how individual cells can keep time. The establishment of the suprachiasmatic nucleus as the master clock showed that in normal circumstances the brain relies on one nucleus to communicate time of day information to the rest of the body and brain. By what method the SCN accomplishes this is largely unknown. Glucocorticoid hormones are known to have a role in this communication, but evidence remains for a neuronal pathway between the SCN and extra SCN ...


Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang 2018 Virginia Commonwealth University

Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang

Theses and Dissertations

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the ...


Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy 2018 Virginia Commonwealth University

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase ...


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