A5012856412- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Traumatic Brain Injury Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Sleep and Wakefulness Research
- Spaceflight effects on biology
- Neuroendocrine regulation and behavior
- Iron Metabolism and Disorders
- Cardiac Arrest and Resuscitation
- Chemical Synthesis and Analysis
- Automotive and Human Injury Biomechanics
- Nicotinic Acetylcholine Receptors Study
- Neural and Behavioral Psychology Studies
- Anesthesia and Neurotoxicity Research
- Radiation Therapy and Dosimetry
- Prenatal Substance Exposure Effects
- Circadian rhythm and melatonin
- Enzyme Structure and Function
- Neurobiology and Insect Physiology Research
- Cannabis and Cannabinoid Research
- Attention Deficit Hyperactivity Disorder
Medical College of Wisconsin
2016-2025
The University of Texas at Austin
2001-2024
North Carolina State University
2020
Pharmacosmos (United States)
2020
Bioscience Research
2015
Institute of Pharmacology
2015
Milwaukee VA Medical Center
2014
Vanderbilt University Medical Center
2006-2012
John F. Kennedy Center for the Performing Arts
2010-2012
Vanderbilt University
2005-2012
The selective serotonergic neurotoxicity of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) depends on their systemic metabolism. We have recently shown that inhibition brain endothelial cell γ-glutamyl transpeptidase (γ-GT) potentiates the both MDMA MDA, indicating metabolites are substrates for this enzyme contribute to neurotoxicity. Consistent with view, glutathione (GSH) <i>N</i>-acetylcysteine conjugates α-methyl dopamine (α-MeDA)...
The bed nucleus of the stria terminalis (BNST) is a key component CNS stress and reward circuit. Synaptic plasticity in this region could part underlie persistent behavioral alterations generalized anxiety addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated stress, addiction, synaptic plasticity, but their roles BNST are unknown. We find that activation group mGluRs dorsal induces depression excitatory transmission through two distinct mechanisms. First,...
Compounds that activate both NOP and mu-opioid receptors might be useful as analgesics drug abuse medications. Studies were carried out to better understand the biological activity of such compounds.Binding affinities determined on membranes from cells transfected with opioid receptors. Functional was by [(35)S]GTPgammaS binding cell using mouse vas deferens preparation in vitro tail flick antinociception assay vivo.Compounds ranged affinity SR14150, 20-fold selective for receptors,...
Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating reinforcing effects of drugs abuse, but not food. The purpose this study was to use mGluR5 knockout (KO), heterozygous (Het), wildtype (WT) mice determine if modulates operant sensation seeking (OSS), an task uses varied sensory stimuli as a reinforcer. We found KO had significantly reduced OSS responding relative WT mice, while Het displayed paradoxical...
From ANNs to NAMs! Data from an experimental metabotropic glutamate receptor 5 (mGlu5) high-throughput screen (HTS) were employed train artificial neural networks (ANNs) based on 345 confirmed negative allosteric modulators (NAMs) and 155 774 inactive compounds. This effort identified two potent mGlu5 NAMs with a unique chemotype. Optimization afforded tool compound (shown), active in mouse models of anxiety addiction. Detailed facts importance specialist readers are published as "Supporting...
Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without previous history of alcohol dependence. Despite this correlational relationship, the extent to which neurological effects mTBI contribute development alcoholism unknown. In study, we used rodent blast exposure model investigate relationship between and voluntary drinking naïve rats. We have previously demonstrated Sprague Dawley rats that leads microstructural abnormalities medial...
Traumatic brain injury (TBI) commonly results in cognitive and psychiatric problems. Cognitive impairments occur approximately 30% of patients suffering from mild TBI (mTBI), correlational evidence clinical studies indicates that substance abuse may be increased following mTBI. However, understanding the lasting problems stemming mTBI is difficult settings where pre-injury assessment not possible or accurate. Therefore, we used a previously characterized blast model (bTBI) to examine...
There is a subset of patients with mild traumatic brain injury (mTBI) who report persistent symptoms that impair their functioning and quality life. Being able to predict which will experience prolonged symptom recovery would help clinicians target resources for clinical follow-up those most in need, facilitate research develop precision medicine treatments mTBI. The purpose this study was investigate the predictors prospective sample emergency department trauma either mTBI or non-mTBI...
Mild traumatic brain injury (mTBI) can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration projectiles. Mechanism is likely influence the type, severity, chronicity outcomes. The objective this study was determine differences in severity time-course behavioral outcomes following blast mTBI. Medical College Wisconsin (MCW) Rotational Injury model shock tube primary were used induce mTBI rats assessments conducted within...
A limitation of simulated space radiation studies is that exposure not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam in absence presence weightlessness using hindlimb unloading (HU) alone. Six following testing 9 irradiation, plasma brain tissues (hippocampus cortex) were processed to determine...
Drugs of abuse affect behavior by altering neuronal communication within the brain. Previous research examining effects intraperitoneally administered cocaine has revealed that alters excitatory glutamatergic signaling, both directly through regulation synaptic function, and indirectly cellular excitability in areas drug reward circuitry such as nucleus accumbens (NAcc) ventral tegmental area. We have now extended these findings testing hypothesis self-administration might elicit similar...
Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, process that is impaired post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice overexpress neurogranin (a calmodulin-binding protein facilitates long-term potentiation) PFC. Neurogranin overexpression PFC enhanced potentiation increased rates extinction learning both fear conditioning sucrose...
Abstract Study objectives The hypothalamic-pituitary-adrenal (HPA) axis is critical in regulating responses to physiological and psychological disturbances. Chronic sleep restriction (SR) interacts with the HPA ways that are poorly delineated. present study evaluated how chronic SR alters pituitary adrenal function. was studied both alone a model of opioid use disorder as potential cause abnormalities during abstinence. Methods After established self-administration oxycodone or saline...
The conformational stability of proteins is typically investigated by use a variety biophysical measurements as function environmental stresses such pH and temperature. Thus, multiple experiments are required on instruments, each providing information particular aspect protein's higher order structural integrity. These require large sample quantities long experimental times. In this study, new methodology described to obtain protein data simultaneously, including UV absorption, light...
Repifermin, a truncated form of fibroblast growth factor-10 (FGF-10) also known as keratinocyte factor-2 (KGF-2), is heparin-binding protein with potent regenerative properties. The unfolds and aggregates at relatively low temperature (~37 °C). Electrostatic interactions between polyanions several FGFs have been reported to enhance the thermal stability these proteins. Polyethylene glycol (PEG) was grafted pentosan polysulfate (PPS) dextran sulfate (DS) an alternative means stabilize...
Each year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters medial prefrontal cortex, an area implicated in addiction, for at least 30 days post injury rats. Repeated exposures result greater physiological behavioral dysfunction than exposure; however, impact repeated on addiction is unknown. In this study, effect...