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Tonic activation of norepinephrine

Mohammad Ebrahimzadeh, Mostafa El Mansari, Pierre Blier
Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophoresis in the rat brain. The firing rate of dopamine (DA) neurons was significantly decreased (26%) after 14, but not 4 days of vortioxetine administration (vortioxetine-containing chow, 1.8 g/kg vortioxetine)...
November 13, 2017: Neuropharmacology
Alessio Dragone, Stefano Lasaponara, Mario Pinto, Francesca Rotondaro, Maria De Luca, Fabrizio Doricchi
fMRI investigations in healthy humans have documented phasic changes in the level of activation of the right temporal-parietal junction (TPJ) during cued voluntary orienting of spatial attention. Cues that correctly predict the position of upcoming targets in the majority of trials, i.e., predictive cues, produce higher deactivation of the right TPJ as compared with non-predictive cues. Since the right TPJ is the recipient of noradrenergic (NE) innervation, it has been hypothesised that changes in the level of TPJ activity are matched with changes in the level of NE activity...
October 3, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Jordan G McCall, Edward R Siuda, Dionnet L Bhatti, Lamley A Lawson, Zoe A McElligott, Garret D Stuber, Michael R Bruchas
Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice...
July 14, 2017: ELife
Dina Lelic, Tine M Hansen, Esben B Mark, Anne E Olesen, Asbjørn M Drewes
INTRODUCTION: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). METHODS: Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b...
September 1, 2017: Neuropharmacology
Christopher M Warren, Robert C Wilson, Nic J van der Wee, Eric J Giltay, Martijn S van Noorden, Jonathan D Cohen, Sander Nieuwenhuis
The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system...
2017: PloS One
Sudarat Nimitvilai, Marcelo F Lopez, Patrick J Mulholland, John J Woodward
Alcohol abuse disorders are associated with dysfunction of frontal cortical areas including the orbitofrontal cortex (OFC). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including alcoholism. However, little is known regarding how monoamines affect OFC neuron excitability or whether this modulation is altered by chronic exposure to ethanol. In this study, we examined the effect of dopamine, norepinephrine, and serotonin on lOFC neuronal excitability in naive mice and in those exposed to chronic intermittent ethanol (CIE) treatment...
August 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Pawel J Winklewski, Marek Radkowski, Magdalena Wszedybyl-Winklewska, Urszula Demkow
Locus coeruleus is a critical component of the brain noradrenergic system. The brain noradrenergic system provides the neural substrate for the architecture supporting the interaction with, and navigation through, an external world complexity. Changes in locus coeruleus tonic and phasic activity and the interplay between norepinephrine and α1- and α2-adrenoceptors in the prefrontal cortex are the key elements of this sophisticated architecture. In this narrative review we discuss how the brain noradrenergic system is affected by increased exposure to corticotropin-releasing hormone triggered by stress response...
2017: Advances in Experimental Medicine and Biology
Young Chul Kim, Dae Hoon Kim, Sang Eok Lee, Chan Hyung Kim, Woong Choi, Sang Jin Lee, Hyo-Yung Yun
OBJECTIVE: Spontaneous oscillation of tone of blood vessel called vasomotion cause vessel to flow blood which is an oscillation of flow into an organ. Microcirculation is sensitive to hypoxic condition and metabolism but mechanism of vasomotion is still poorly understood. DESIGN AND METHOD: Purpose: We studied involvement of metabolism-mediated regulation by intracellular ATP level of vasomotion in human gastric artery. METHODS: Conventional contractile measuring system and Western blot were used...
September 2016: Journal of Hypertension
Young Chul Kim, Dae Hoon Kim, Sang Eok Lee, Chan Hyung Kim, Woong Choi, Sang Jin Lee, Hyo-Yung Yun
OBJECTIVE: Spontaneous oscillation of tone of blood vessel called vasomotion cause vessel to flow blood which is an oscillation of flow into an organ. Microcirculation is sensitive to hypoxic condition and metabolism but mechanism of vasomotion is still poorly understood. DESIGN AND METHOD: HASH(0x4d89d88) PURPOSE: We studied involvement of metabolism-mediated regulation by intracellular ATP level of vasomotion in human gastric artery. METHODS: Conventional contractile measuring system and Western blot were used...
September 2016: Journal of Hypertension
Marco Atzori, Roberto Cuevas-Olguin, Eric Esquivel-Rendon, Francisco Garcia-Oscos, Roberto C Salgado-Delgado, Nadia Saderi, Marcela Miranda-Morales, Mario Treviño, Juan C Pineda, Humberto Salgado
Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework...
2016: Frontiers in Synaptic Neuroscience
Yan-Yuen Poon, Ching-Yi Tsai, Chung-Dar Cheng, Alice Y W Chang, Samuel H H Chan
The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
David Sulzer, Stephanie J Cragg, Margaret E Rice
Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved...
August 2016: Basal Ganglia
A J Parent, P Tétreault, M Roux, K Belleville, J-M Longpré, N Beaudet, P Goffaux, P Sarret
Clinical evidences suggest that an imbalance between descending inhibition and facilitation drives the development of chronic pain. However, potential mechanisms promoting the establishment of a persistent pain state and the increased pain vulnerability remain unknown. This preclinical study was designed to evaluate temporal changes in descending pain modulation at specific experimental endpoints (12, 28, 90 and 168 days) using a novel double-hit model of chronic/tonic pain (first hit: chronic constriction injury (CCI) model; second hit: tonic formalin pain in the contralateral hindpaw)...
February 19, 2016: Neuroscience
Norah Essali, Jeff Sanders
Norepinephrine is a neurotransmitter that signals by stimulating the α1, α2 and β adrenergic receptor (AR). We determined the role of these receptors in regulating the immediate early genes, Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 in the rat cerebral cortex. RX821002, an α2-AR antagonist, produced Arc and Zif268 elevations across cortical layers. Next we examined the effects of delivering RX821002 with an α1-AR antagonist, prazosin, and a β-AR antagonist, propranolol. RX821002 given with a prazosin and propranolol cocktail, or with each of these antagonists individually, decreased Arc and Zif268 to saline-treated control levels in most cortical layers...
January 26, 2016: Neuroscience Letters
Awanish Mishra, Jasmine Kaur Punia, Chris Bladen, Gerald W Zamponi, Rajesh Kumar Goel
Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms...
2015: Channels
O O Vinogradova, P I Yanchuk, O M Pasichnichenko
Effects of picotamide and zileuton on tonic contractile activity of the rat portal vein preparations, induced by acetylcholine (2.10(-5) mol/1) and phenylephrine (5.10(-7) mol/1) were investigated. Conversion of arachidonic acid products (prostaglandins, leukotrienes) synthesized by endothelial cells, plays an important role in the local regulation of vascular tone. The compounds formed in a cascade of enzymatic transformations can modulate the effect of other vasoactive factors. Picotamide (6,5.10(-5) mol/1) - thromboxane receptor and thromboxane -synthase blocker - depress acetylcholine-induction tonic contraction of isolated segments of portal vein with intact endothelium by 29% and norepinephrine-induction reduction of 45% relative to the control values...
2015: Fiziolohichnyĭ Zhurnal
Mostafa El Mansari, Agnes Crnic, Chris Oosterhof, Pierre Blier
Vilazodone has high affinity for the human 5-hydroxytryptamine1A (h5-HT1A) receptor and for the serotonin transporter (5-HTT). A previous in vivo microdialysis experiment showed that a single administration of vilazodone, dose-dependently increases extracellular 5-HT but not norepinephrine (NE) or dopamine (DA) levels in rat medial prefrontal cortex and ventral hippocampus. The effects of vilazodone on monoaminergic systems were assessed using single-unit extracellular recordings and microiontophoresis in the rat brain...
December 2015: Neuropharmacology
Gerard A Zitnik, Andrè L Curtis, Susan K Wood, Jay Arner, Rita J Valentino
Early life stress is associated with the development of psychiatric disorders. Because the locus coeruleus-norepinephrine (LC-NE) system is a major stress-response system that is implicated in psychopathology, developmental differences in the response of this system to stress may contribute to increased vulnerability. Here LC single unit and network activity were compared between adult and adolescent rats during resident-intruder stress. In some rats, LC and medial prefrontal cortex (mPFC) coherence was quantified...
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Yajie Sun, Sarah Hunt, Pankaj Sah
Norepinephrine and corticotropin-releasing hormone (CRH) have long been implicated in the response to stress. In this issue of Neuron, McCall et al. (2015) show that CRH projections from the central amygdala drive tonic locus coeruleus activity that evokes acute anxiety responses and place aversion.
August 5, 2015: Neuron
Scott D Gleason, Akihiko Kato, Hai H Bui, Linda K Thompson, Sabrina N Valli, Patrick V Stutz, Ming-Shang Kuo, Julie F Falcone, Wesley H Anderson, Xia Li, Jeffrey M Witkin
Transmembrane AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor regulatory protein (TARP) γ-8 is an auxiliary protein associated with some AMPA receptors. Most strikingly, AMPA receptors associated with this TARP have a relatively high localization in the hippocampus. TARP γ-8 also modifies the pharmacology and trafficking of AMPA receptors. However, to date there is little understanding of the biological significance of this auxiliary protein. In the present set of studies we provide a characterization of the differential pharmacology and behavioral consequences of deletion of TARP γ-8 by comparing the wild type (WT) and γ-8 -/- (knock-out, KO) mouse...
2015: CNS & Neurological Disorders Drug Targets
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