461 results match your criteria: "Center for Neuropharmacology[Affiliation]"

Article Synopsis
  • - With the rise of cannabis legalization globally, there's a growing concern about increased cannabis use and cannabis use disorder (CUD), highlighting the urgent need for effective treatment options.
  • - This review assesses various promising medications for CUD, focusing on their mechanisms like targeting cannabinoid receptors, serotonin pathways, and GABA activity, and organizes results based on symptoms like withdrawal and craving.
  • - The study also emphasizes the importance of considering priority populations—such as women and different racial/ethnic groups—when researching treatment outcomes, as they may experience CUD differently due to various factors.
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Background: Neurorehabilitation in military populations is complicated by higher rates of PTSD and unique characteristics of military institutions. These factors can adversely impact the patient-therapist therapeutic alliance and engagement with the rehabilitation process leading to poorer outcomes. MDMA is a non-classical psychedelic with pro-social and fear regulating properties.

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Aminergic nuclei in mammals are generally composed of relatively small numbers of cells with broad projection patterns. Despite the gross similarity of many individual neurons, recent transcriptomic, anatomic and behavioral studies suggest previously unsuspected diversity. Smaller clusters of aminergic neurons in the model organism provide an opportunity to explore the ramifications of neuronal diversity at the level of individual cells.

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This perspective encompasses a focused review of the literature leading to a tipping point in electroanalytical chemistry. We tie together the threads of a "revolution" quietly in the making for years through the work of many authors. Long-held misconceptions about the use of background subtraction in fast voltammetry are addressed.

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Unveiling the link between chronic pain and misuse of opioids and cannabis.

J Neural Transm (Vienna)

May 2024

MacDonald Research Laboratory Building, Department of Psychiatry and Biobehavioral Sciences, Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E Young Drive South, Office 2774, Los Angeles, CA, 90095, USA.

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse.

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Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty.

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Neuroinflammation drives sex-dependent effects on pain and negative affect in a murine model of repeated mild traumatic brain injury.

Pain

April 2024

Department of Psychiatry & Biobehavioral Sciences, Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, United States.

The Center for Disease Control and Prevention estimates that 75% of reported cases of traumatic brain injury (TBI) are mild, where chronic pain and depression are 2 of the most common symptoms. In this study, we used a murine model of repeated mild TBI to characterize the associated pain hypersensitivity and affective-like behavior and to what extent microglial reactivity contributes to these behavioral phenotypes. Male and female C57BL/6J mice underwent sham or repeated mild traumatic brain injury (rmTBI) and were tested for up to 9 weeks postinjury, where an anti-inflammatory/neuroprotective drug (minocycline) was introduced at 5 weeks postinjury in the drinking water.

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Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.

J Parkinsons Dis

November 2023

Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Background: Evidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression.

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Aptameric receptors are important biosensor components, yet our ability to identify them depends on the target structures. We analyzed the contributions of individual functional groups on small molecules to binding within 27 target-aptamer pairs, identifying potential hindrances to receptor isolation-for example, negative cooperativity between sterically hindered functional groups. To increase the probability of aptamer isolation for important targets, such as leucine and voriconazole, for which multiple previous selection attempts failed, we designed tailored strategies focused on overcoming individual structural barriers to successful selections.

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Alcohol use disorder (AUD) is characterized by loss of intake control, increased anxiety, and susceptibility to relapse inducing stressors. Both astrocytes and neurons contribute to behavioral and hormonal consequences of chronic intermittent ethanol (CIE) exposure in animal models. Details on how CIE disrupts hypothalamic neuro-glial communication, which mediates stress responses are lacking.

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Introduction: We used a home-based (HB) post-vasectomy semen analysis (PVSA) between 2014 and 2017, but we have since reverted to local lab-based (LB) testing. In this study, we compared PVSA compliance rates in HB and LB test settings and describe factors that may influence completion rates.

Methods: We retrospectively identified patients who underwent vasectomy at our institution.

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Technology Roadmap for Flexible Sensors.

ACS Nano

March 2023

Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited.

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Flexible and Implantable Polyimide Aptamer-Field-Effect Transistor Biosensors.

ACS Sens

December 2022

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.

Monitoring neurochemical signaling across time scales is critical to understanding how brains encode and store information. Flexible (vs stiff) devices have been shown to improve monitoring, particularly over longer times, by reducing tissue damage and immunological responses. Here, we report our initial steps toward developing flexible and implantable neuroprobes with aptamer-field-effect transistor (FET) biosensors for neurotransmitter monitoring.

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Opioid Systems and Depression: The Relationship Is Strengthening.

Biol Psychiatry

December 2022

Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California. Electronic address:

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Alcohol and substance use disorders are heterogeneous conditions with limited effective treatment options. While there have been prior attempts to classify addiction subtypes, they have not been translated into clinical practice. In an effort to better understand heterogeneity in psychiatric disorders, the National Institute for Mental Health Research Domain Criteria (RDoC) has challenged scientists to think beyond diagnostic symptoms and to consider the underlying features of psychopathology from a neuroscience-based framework.

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Regulation of oviduct muscle contractility by octopamine.

iScience

August 2022

Department of Psychiatry and Biobehavioral Sciences, Hatos Center for Neuropharmacology, Gonda (Goldschmied) Neuroscience and Genetics Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Octopamine is essential for egg-laying in , but the neuronal pathways and receptors by which it regulates visceral muscles in the reproductive tract are not known. We find that the two octopamine receptors that have been previously implicated in egg-laying- and -are expressed in octopaminergic and glutamatergic neurons that project to the reproductive tract, peripheral ppk(+) neurons within the reproductive tract and epithelial cells that line the lumen of the oviducts. Further optogenetic and mutational analyses indicate that octopamine regulates both oviduct contraction and relaxation via and respectively.

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Aims: The current study examined the association between pain catastrophizing and alcohol cue-elicited brain activation in individuals with alcohol use disorder (AUD).

Methods: Non-treatment seeking heavy drinkers with AUD (n = 45; 28 males) completed self-report measures of pain catastrophizing and alcohol use/problems as part of a clinical trial of the neuroimmune modulator ibudilast. Participants were randomized to either placebo (n = 25) or ibudilast (n = 20) and completed an functional magnetic resonance imaging (fMRI) scan to assess neural activation to alcohol cues 1 week into the medication trial.

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During threat exposure, survival depends on defensive reactions. Prior works linked large glutamatergic populations in the midbrain periaqueductal gray (PAG) to defensive freezing and flight, and established that the overarching functional organization axis of the PAG is along anatomically-defined columns. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing.

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Optogenetic Stimulation of Midbrain Dopamine Neurons Produces Striatal Serotonin Release.

ACS Chem Neurosci

April 2022

Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, California 90095, United States.

Targeting neurons with light-driven opsins is widely used to investigate cell-specific responses. We transfected midbrain dopamine neurons with the excitatory opsin Chrimson. Extracellular basal and stimulated neurotransmitter levels in the dorsal striatum were measured by microdialysis in awake mice.

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and Characterization of a Partial Mu Opioid Receptor Agonist, NKTR-181, Supports Future Therapeutic Development.

Front Pain Res (Lausanne)

August 2021

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States.

Mu opioid receptor (MOPr) agonists are well-known and frequently used clinical analgesics but are also rewarding due to their highly addictive and often abusive properties. This may lead to opioid use disorder (OUD) a disorder that effects millions of people worldwide. Therefore, novel compounds are urgently needed to treat OUD.

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Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring.

Sci Adv

January 2022

Interconnected and Integrated Bioelectronics Lab (IBL), Department of Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges.

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Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome.

J Neurosci

January 2022

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.

We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number.

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While tools for monitoring in vivo electrophysiology have been extensively developed, neurochemical recording technologies remain limited. Nevertheless, chemical communication via neurotransmitters plays central roles in brain information processing. We developed implantable aptamer–field-effect transistor (FET) neuroprobes for monitoring neurotransmitters.

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Many voltammetry methods have been developed to monitor brain extracellular dopamine levels. Fewer approaches have been successful in detecting serotonin in vivo. No voltammetric techniques are currently available to monitor both neurotransmitters simultaneously across timescales, even though they play integrated roles in modulating behavior.

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A photoswitchable GPCR-based opsin for presynaptic inhibition.

Neuron

June 2021

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA. Electronic address:

Optical manipulations of genetically defined cell types have generated significant insights into the dynamics of neural circuits. While optogenetic activation has been relatively straightforward, rapid and reversible synaptic inhibition has proven more elusive. Here, we leveraged the natural ability of inhibitory presynaptic GPCRs to suppress synaptic transmission and characterize parapinopsin (PPO) as a GPCR-based opsin for terminal inhibition.

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