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Gaba a antagonist

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https://www.readbyqxmd.com/read/28546770/reduced-gabaergic-neuronal-activity-in-zona-incerta-causes-neuropathic-pain-in-a-rat-sciatic-nerve-chronic-constriction-injury-model
#1
Hyeong Cheol Moon, Young Seok Park
PURPOSE: The zona incerta (ZI) is below the ventral tier of the thalamus and has a strong influence selectively in higher-order thalamic relays. Although neuropathic pain has been suggested to result from reduced gamma-aminobutyric acid (GABA) and GABAergic signaling in the ZI, the mechanisms remain unclear. Here, the role of GABA and GABAergic signaling was investigated in the ZI in neuropathic pain using sciatic nerve chronic constriction injury (CCI) rats. MATERIALS AND METHODS: Single-unit neuronal activity was recorded, and microdialysis was performed in the ZI of CCI rats and sham-treated rats in vivo...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#2
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479740/effect-of-shankhpushpi-on-alcohol-addiction-in-mice
#3
Mahi Heba, Sana Faraz, Sugato Banerjee
Alcohol addiction is a worldwide problem. It has mainly two components: dependence and withdrawal. Characteristic properties of most anti-addictive compounds include anti-anxiety, anticonvulsant, antidepressant, and nootropic actions. Shankhpushpi (Convolvulus pluricaulis. Convolvulaceae), known ethnopharmacologically as brain tonic, possess all the properties mentioned above. Here, we screen shankhpushpi for possible anti-addictive potential. Effect of shankhpushpi churna was measured on ethanol withdrawal anxiety using elevated plus maze...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28477384/cognitive-deficits-caused-by-prefrontal-cortical-and-hippocampal-neural-disinhibition
#4
REVIEW
Tobias Bast, Marie Pezze, Stephanie McGarrity
We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and hippocampus for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline...
May 6, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28456768/corticotropin-releasing-factor-receptor-1-antagonist-differentially-inhibits-freezing-behavior-and-changes-gamma-aminobutyric-acidergic-activity-in-the-amygdala-in-low-and-high-anxiety-rats
#5
A Skorzewska, A Wislowska-Stanek, M Lehner, D Turzynska, A Sobolewska, P Krzascik, A Plaznik
The aim of this study was to examine the effects of non-peptide corticotropin-releasing factor receptor 1 (CRF1) antagonist (antalarmin) administration on rat conditioned fear responses and gamma-aminobutyric acid (GABA)-ergic brain activity (GAD67 expression and GABA concentration) in low-anxiety (LR) and high-anxiety (HR) rats. The animals were divided into the LR and HR groups based on the duration of their conditioned freezing response in the first contextual fear test. After 28 days, the animals were re-subjected to the contextual fear training and test...
February 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28448525/brorin-is-required-for-neurogenesis-gliogenesis-and-commissural-axon-guidance-in-the-zebrafish-forebrain
#6
Ayumi Miyake, Yoko Mekata, Hidenori Fujibayashi, Kazuya Nakanishi, Morichika Konishi, Nobuyuki Itoh
Bmps regulate numerous neural functions with their regulators. We previously identified Brorin, a neural-specific secreted antagonist of Bmp signaling, in humans, mice, and zebrafish. Mouse Brorin has two cysteine-rich domains containing 10 cysteine residues in its core region, and these are located in similar positions to those in the cysteine-rich domains of Chordin family members, which are secreted Bmp antagonists. Zebrafish Brorin had two cysteine-rich domains with high similarity to those of mouse Brorin...
2017: PloS One
https://www.readbyqxmd.com/read/28444767/the-dual-orexin-receptor-antagonist-dora-22-lowers-histamine-levels-in-the-lateral-hypothalamus-and-prefrontal-cortex-without-lowering-hippocampal-acetylcholine
#7
Lihang Leon Yao, Andres Ramirez, Anthony J Roecker, Steven Fox, Jason Uslaner, Sean M Smith, Robert Hodgson, Paul J Coleman, John J Renger, Christopher J Winrow, Anthony L Gotter
Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA)A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28442196/mechanism-of-neuronal-activity-and-synaptic-transmission-in-rostral-ventrolateral-medulla
#8
Liangchen Zhao, Tianji Liu, Rutao Xu, Liu He, Man Duan, Dejun Xu
Rostral ventrolateral medulla (RVLM) plays an essential role in blood pressure homeostasis. This study was aimed to investigate the mechanism of neuronal activity and synaptic transmission in the RVLM. Medulla oblongata slices were carefully obtained from brainstem of rats. With continues perfusion of artificial cerebrospinal fluid (ACSF), the spontaneous firing of slices and amplitudes were assayed by conventional whole cell patch-clamp recording after addition of gamma-aminobutyric acid (GABA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl d-aspartate (NMDA)...
April 22, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28438981/acute-inflammation-reveals-gabaa-receptor-mediated-nociception-in-mouse-dorsal-root-ganglion-neurons-via-pge2-receptor-4-signaling
#9
In Jeong Jang, Alexander J Davies, Nozomi Akimoto, Seung Keun Back, Pa Reum Lee, Heung Sik Na, Hidemasa Furue, Sung Jun Jung, Yong Ho Kim, Seog Bae Oh
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl(-) permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28436443/curcumol-allosterically-modulates-gaba-a-receptors-in-a-manner-distinct-from-benzodiazepines
#10
Yan-Mei Liu, Hui-Ran Fan, Jing Ding, Chen Huang, Shining Deng, Tailin Zhu, Tian-Le Xu, Wei-Hong Ge, Wei-Guang Li, Fei Li
Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428755/pharmacological-analysis-of-the-anti-epileptic-mechanisms-of-fenfluramine-in-scn1a-mutant-zebrafish
#11
Jo Sourbron, Ilse Smolders, Peter de Witte, Lieven Lagae
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428226/rapid-throughput-analysis-of-gabaa-receptor-subtype-modulators-and-blockers-using-disbac1-3-membrane-potential-red-dye
#12
Atefeh Mousavi Nik, Brandon Pressly, Vikrant Singh, Shane Antrobus, Susan Hulsizer, Michael A Rogawski, Heike Wulff, Isaac N Pessah
Fluorometric Imaging Plate Reader (FLIPR®) membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high throughput drug screening for G-protein coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABAA receptor (GABAAR) isoforms (synaptic α1β3γ2, extrasynaptic α4β3δ, and β3 homopentomers). High-resolution mass spectrometry identified FMP-Red-dye as DisSBAC1(3). GABAAR expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane (Em) potentials compared to GABAAR-null cells...
April 20, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28424576/defensive-vocalizations-and-motor-asymmetry-triggered-by-disinhibition-of-the-periaqueductal-gray-in-non-human-primates
#13
Patrick A Forcelli, Hannah F Waguespack, Ludise Malkova
Rapid and reflexive responses to threats are present across phylogeny. The neural circuitry mediating reflexive defense reactions has been well-characterized in a variety of species, for example, in rodents and cats, the detection of and species-typical response to threats is mediated by a network of structures including the midbrain tectum (deep and intermediate layers of the superior colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as the amygdala and hypothalamus. However, relatively little is known about the functional architecture of defense circuitry in primates...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#14
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#15
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28419057/gabaergic-modulation-of-noradrenaline-release-caused-by-blood-pressure-changes-in-the-rat-median-preoptic-area
#16
Makoto Takahashi, Junichi Tanaka
Experiments using in-vivo microdialysis methods were conducted to investigate whether blood pressure changes cause an alteration in the release of noradrenaline (NA) in the median preoptic nucleus (MnPO) and whether the γ-aminobutyric acid (GABA) receptor mechanism is involved in the modulation of the pressure response-induced alteration in the NA release. In urethane-anesthetized male rats, intravenous administration of metaraminol, an α-agonist, significantly produced an increase in dialysate NA concentration in the MnPO area accompanied by an elevation in the mean arterial pressure (MAP)...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28412500/the-major-neurotransmitter-systems-in-the-basolateral-amygdala-and-the-ventral-tegmental-area-mediate-morphine-induced-memory-consolidation-impairment
#17
Khadijeh Alsadat Sharifi, Ameneh Rezayof, Anahita Torkaman-Boutorabi, Mohammad-Reza Zarrindast
In the present study, we investigated the possible participation of the endocannabinoid system in the basolateral amygdala and N-methyl-d-aspartate (NMDA) or GABA-A receptor neurotransmission in the ventral tegmental area in the memory consolidation impairment induced by morphine administration. To measure memory formation, step-through type passive avoidance apparatus was used with adult male Wistar rats. The results showed that intraperitoneal (i.p.) administration of morphine (3 and 6mg/kg) after the successful training phase had an amnestic effect and induced memory consolidation impairment...
April 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28411234/phenotype-of-gaba-transaminase-deficiency
#18
Mary Kay Koenig, Ryan Hodgeman, James J Riviello, Wendy Chung, Jennifer Bain, Claudia A Chiriboga, Kazushi Ichikawa, Hitoshi Osaka, Megumi Tsuji, K Michael Gibson, Penelope E Bonnen, Phillip L Pearl
OBJECTIVE: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype. METHODS: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil. RESULTS: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth...
April 14, 2017: Neurology
https://www.readbyqxmd.com/read/28394853/targeting-brain-derived-neurotrophic-factor-in-the-medial-thalamus-for-the-treatment-of-central-poststroke-pain-in-a-rodent-model
#19
Hsi-Chien Shih, Yung-Hui Kuan, Bai-Chung Shyu
Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area...
May 10, 2017: Pain
https://www.readbyqxmd.com/read/28389811/general-anesthetic-actions-on-gabaa-receptors-in-vivo-are-reduced-in-phospholipase-c-related-catalytically-inactive-protein-knockout-mice
#20
Masaki Hayashiuchi, Tomoya Kitayama, Katsuya Morita, Yosuke Yamawaki, Kana Oue, Taiga Yoshinaka, Satoshi Asano, Kae Harada, Youngnam Kang, Masato Hirata, Masahiro Irifune, Mitsugi Okada, Takashi Kanematsu
PURPOSE: The aim of this study was to investigate the action of general anesthetics in phospholipase C-related catalytically inactive protein (PRIP)-knockout (KO) mice that alter GABAA receptor signaling. METHODS: PRIP regulates the intracellular trafficking of β subunit-containing GABAA receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via β subunit-containing GABAA receptors, in wild-type and Prip-KO mice...
April 7, 2017: Journal of Anesthesia
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