A5086522965- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Treatment of Major Depression
- Photoreceptor and optogenetics research
- Neuropeptides and Animal Physiology
- Biochemical Analysis and Sensing Techniques
- Memory and Neural Mechanisms
- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Pharmacological Receptor Mechanisms and Effects
- Neural dynamics and brain function
- Functional Brain Connectivity Studies
- Diet and metabolism studies
- Cannabis and Cannabinoid Research
- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Neural and Behavioral Psychology Studies
- Computational Drug Discovery Methods
- COVID-19 Clinical Research Studies
- Eating Disorders and Behaviors
- Attention Deficit Hyperactivity Disorder
- Neurological disorders and treatments
- Trace Elements in Health
Johns Hopkins Medicine
2017-2025
Johns Hopkins University
2008-2025
National Institute on Drug Abuse
2016-2025
National Institutes of Health
2007-2024
Instituto Multidisciplinario de Biología Celular
2023
Baylor College of Medicine
2023
National Institute on Alcohol Abuse and Alcoholism
2007-2023
Universitat de Barcelona
2023
Institut de Biomedicina de la Universitat de Barcelona
2023
Scripps Research Institute
2023
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. posits the use "designer receptors," which are drug" clozapine N-oxide (CNO). Nevertheless, vivo mechanism action CNO at DREADDs has never been confirmed. does not enter brain after systemic drug injections and shows low affinity DREADDs. Clozapine, to rapidly converts vivo, high potency. Upon injections,...
Abstract Designer Receptors Exclusively Activated by Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential human applications as well. The prototypical DREADD agonist clozapine N- oxide (CNO) lacks brain entry and converts to clozapine, making it difficult apply basic translational applications. Here we report the development two novel agonists, JHU37152 JHU37160, first dedicated 18 F positron emission...
Improved agonists for chemogenetics Targeting ligand-responsive receptors to specific groups of cells, a strategy known as chemogenetics, is powerful tool in many neurological applications. There increasing interest extending these tools human treatment. Magnus et al. designed chemogenetic ion channels that improve currently available systems and are activated by the clinically used antismoking drug varenicline. They engineered ligand-binding domain less responsive endogenous signals...
We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate relapse seeking during abstinence. Here we studied role nucleus accumbens (NAc) dopamine receptor (Drd)1- Drd2-expressing neurons in self-administration seeking. trained self-administer intruders (9 d, 12 trials/d) tested them on abstinence Day 1. used immunohistochemistry <i>in situ</i> hybridization measure neuronal...
Traditional methods for site-specific drug delivery in the brain are slow, invasive, and difficult to interface with recordings of neural activity. Here, we demonstrate feasibility experimental advantages vivo photopharmacology using "caged" opioid drugs that activated light after systemic administration an inactive form. To enable bidirectional manipulations endogenous receptors vivo, developed photoactivatable oxymorphone (PhOX) naloxone (PhNX), variants mu receptor agonist antagonist...
Subanesthetic ketamine is increasingly used for the treatment of varied psychiatric conditions, both on- and off-label. While it commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture ketamine's mechanistic underpinnings incomplete. Recent clinical evidence has indicated, controversially, that a component efficacy subanesthetic may be opioid dependent. Using pharmacological functional ultrasound imaging in rats, we found blocking receptors suppressed...
Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects non human primates after chronic exposures. Prior studies had shown that upregulation the nucleus accumbens (NAc) rodents trained self-administer alcohol markedly attenuated preference intake. Here we assess effects NAc on intake rats Following 2 weeks i.v....
Abstract Introduction: Dopamine (DA) regulates food intake by modulating reward and motivation but its involvement in obesity is much less understood. Recent evidence points to the of leptin DA‐related modulation intake. Here we assess DA D2 receptors (D2R) a genetic rodent model characterized leptin‐receptor deficiency influence restriction on these receptors. Methods: We compared D2R levels between Zucker Obese (fa/fa) Lean (Fa/Fa) rats at 1 4 months age two different feeding conditions...
The ability to map the functional connectivity of discrete cell types in intact mammalian brain during behavior is crucial for advancing our understanding function normal and disease states. We combined designer receptor exclusively activated by drug (DREADD) technology behavioral imaging with μPET [18F]fluorodeoxyglucose (FDG) generate whole-brain metabolic maps cell-specific circuits awake, freely moving state. have termed this approach DREADD-assisted mapping (DREAMM) documented its rats...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme as its primary infection mechanism. Interactions between S and endogenous proteins occur after but are not well understood. We profiled binding of against >9000 human found an interaction estrogen receptor α (ERα). Using bioinformatics, supercomputing, experimental assays, we identified a highly conserved functional nuclear coregulator (NRC) LXD-like motif on the S2...
<i>Background:</i> The dopamine (DA) D<sub>2</sub> receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models increases lean muscle mass, improves glucose intolerance insulin resistance, reduces triglycerides free fatty acids. We have previously shown a negative correlation between D2R weight obese individuals rodents, that chronic food restriction binding genetically rats. purpose of this study was to assess whether the antiobesity...
Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose was used to measure changes in regional brain glucose metabolism (BGluM) response optogenetic stimulation (using the excitatory channelrhodopsin-2) of nucleus accumbens (NAc) awake rats. We demonstrated not only increases BGluM that correlated c-Fos expression region stimulation, but also ipsilateral striatum, periaqueductal gray, and somatosensory cortex, contralateral amygdala, ventral pallidum, globus pallidus,...