A5090382498- Neurotransmitter Receptor Influence on Behavior
- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Biochemical effects in animals
- Psychedelics and Drug Studies
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Receptor Mechanisms and Effects
- Intensive Care Unit Cognitive Disorders
- Acupuncture Treatment Research Studies
- Lipid metabolism and biosynthesis
- Circadian rhythm and melatonin
- Diet and metabolism studies
- Forensic Toxicology and Drug Analysis
- Opioid Use Disorder Treatment
- Memory and Neural Mechanisms
- Pharmacology and Obesity Treatment
- Clostridium difficile and Clostridium perfringens research
- Fatty Acid Research and Health
- GABA and Rice Research
- Adipose Tissue and Metabolism
- Anesthesia and Neurotoxicity Research
- Chemical synthesis and alkaloids
- Gut microbiota and health
- Genetic Neurodegenerative Diseases
Indiana University Bloomington
2019-2025
Indiana University
2024
University of Colorado Anschutz Medical Campus
2019
Brigham Young University
2017-2018
Protein-protein interaction inhibitor of the sodium NaV1.7 channel has analgesic effects in preclinical models pain.
Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance dependence. In present study, we investigated influence on opioid withdrawal by evaluating fecal microbiota transplantation (FMT), antibiotic probiotic treatments, pharmacological inhibition permeability in a mouse model Repeated intraperitoneal (i.p.) morphine treatment...
Abstract Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These induce cognitive, motor, behavioral deficits that can last for months even years with an increased risk of dementia, Parkinson’s disease, chronic traumatic encephalopathy. There is no approved medical treatment these types injuries. To this end, we tested the healing effects psychedelic psilocybin, as it known to...
Abstract Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This the first study to use MRI follow functional changes in brain activity response different doses of psilocybin fully awake, drug naive rats. Female male rats were given IP injections vehicle or 0.03 mg/kg, 0.3 3.0 mg/kg while awake during imaging session. Changes BOLD signal recorded over 20 min window. Data for resting state connectivity collected approximately 35 post injection All data...
The nutrient sensor farnesoid X receptor (FXR) transcriptionally regulates whole-body lipid and glucose homeostasis. Several studies examined targeting FXR as a modality to treat obesity with varying conflicting results, emphasizing the need study tissue-specific roles of FXR. We show that deletion adipocyte Fxr results in increased hypertrophy suppression several metabolic genes is akin some changes noted high fat diet (HFD)-fed control mice. Moreover, upon challenge, these effects are...
Though acetaminophen is a ubiquitous analgesic, its mechanism of action remains unknown. Thus, even though causes ~500 deaths each year in the US it has not been possible to design safer alternatives. Because endocannabinoids may have role action, we examined interactions between two. We now report that inhibits activity diacylglycerol lipase α (DAGLα), but DAGLβ decreasing production endocannabinoid 2-arachidonoyl glycerol. This gave rise counterintuitive hypothesis by DAGLα inhibition be...
The endogenous opioid and cannabinoid (endocannabinoid) systems are highly interconnected in the context of drug reward. Bioactive lipids known as N -acylethanolamines (NAEs), and, specifically, anandamide (AEA), influence several unwanted side effects opioids, including dependence tolerance. AEA undergoes degradation by enzyme fatty-acid amide hydrolase (FAAH), whereas biosynthesis vivo is catalyzed -acyl phosphatidylethanolamine phospholipase-D (NAPE-PLD). FAAH implicated reward, but...
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This the first study to use MRI follow functional changes in brain activity response different doses of psilocybin fully awake, drug naive rats. We hypothesized that would show dose-dependent increase prefrontal cortex thalamus, while decreasing hippocampal activity. Female male rats were given IP injections vehicle or 0.03 mg/kg, 0.3 3.0 mg/kg awake during imaging session. These levels validated by measuring...
Acetaminophen (paracetamol) is a common analgesic, but its mechanism of action remains unknown. Despite causing around 500 deaths annually in the US, safer alternatives have not been developed. Because endocannabinoids may role acetaminophen action, we examine interactions between two. We report that inhibits activity diacylglycerol lipase α (DAGLα), DAGLβ, decreasing production endocannabinoid 2-arachidonoyl glycerol. This gives rise to counterintuitive hypothesis by DAGLα inhibition be...
Blockade of cannabinoid type 1 (CB1)-receptor signaling decreases the rewarding properties many drugs abuse and has been proposed as an anti-addiction strategy. However, psychiatric side-effects limit clinical potential orthosteric CB1 antagonists. Negative allosteric modulators (NAMs) represent a novel indirect approach to attenuate by decreasing affinity and/or efficacy ligands. We hypothesized that CB1-NAM would block opioid reward while avoiding unwanted effects GAT358, CB1-NAM, failed...
The neural mechanisms underlying alcohol dependence are not well understood. GABAergic neurons in the ventral tegmental area (VTA) a relevant target for ethanol. They inhibited by ethanol at physiologically-relevant levels vivo and display marked hyperexcitability during withdrawal. In present study, we examined effects of role GABA(A) receptor agonist muscimol on VTA GABA ex following withdrawal from acute chronic exposure. We used standard cell-attached mode electrophysiology slice...
The present studies were undertaken to understand the effects of commonly used nutraceutical PEA on brain function and lipid chemistry. These using MRI broad-scale lipidomics are without precedent in animal or human research. During scanning session awake rats given one three doses (3, 10, 30 mg/kg) vehicle imaged for changes BOLD signal functional connectivity. There was an inverse dose-response negative suggesting a decrease activity affecting prefrontal ctx, sensorimotor cortices, basal...
Abstract Dopamine (DA) neuron excitability is regulated by inhibitory GABAergic synaptic transmission and modulated nicotinic acetylcholine receptors (nAChRs). The aim of this study was to evaluate the role α6 subunit‐containing nAChRs (α6*‐nAChRs) in acute ethanol effects on ventral tegmental area (VTA) GABA DA neurons. α6*‐nAChRs were visualized terminals VTA neurons, α6*‐nAChR transcripts expressed most but only a minority neurons from GAD67 GFP mice. Low concentrations (1–10 mM) enhanced...
Abstract Visual exposure to dim, green, light has been found reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green was due central release endogenous opioids a reduction inflammatory cytokines cerebrospinal fluid. The present study assessed therapy (GLT) on joint rat model osteoarthritis (OA) investigated role endolipids. Male female Wistar rats (207-318 g) received an intra-articular injection...
The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity ion channel excitability this area, which strong implication drug abuse. We recently provided electrophysiological pharmacological evidence that the CaV3.1 isoform T-type voltage-gated calcium channels contributes to VTA dopamine (DA) neurons. However, role T-channels gamma-amino-butyric acid (GABA) neurons remained unaddressed. Here, with...
The endocannabinoid (eCB) system regulates stress responsiveness and hypothalamic-pituitary-adrenal (HPA) axis activity. enzyme
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement transmission represents a potential analgesic strategy. However, therapeutic current GABA agonists and modulators limited by unwanted side effects. We postulated that GABA’s degradation enzyme, aminotransferase (GABA-AT), would increase endogenous levels produce analgesia. evaluated antinociceptive efficacy the potent GABA-AT inhibitor OV329 in rodent models neuropathic inflammatory pain...