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Gaba a antagonist

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https://www.readbyqxmd.com/read/28324056/gabaergic-neurons-and-their-modulatory-effects-on-gnrh3-in-zebrafish
#1
Yanlong Song, Binbin Tao, Ji Chen, Shaoting Jia, Zuoyan Zhu, Vance L Trudeau, Wei Hu
Gamma-aminobutyric acid (GABA) is a major amino acid neurotransmitter in the vertebrate brain. To provide detailed information on the distribution of the GABA in zebrafish (Danio rerio), neurons were labeled with mCherry driven by the glutamic acid decarboxylase 67 (gad67) promoter. In the transgenic line Tg(gad67:mCherry), mCherry-positive gad67 cell bodies were predominantly localized to the olfactory bulb, pallial zones, subpallium zones, parvocellular preoptic nucleus, periventricular gray zone of optic tectum, torus semicircularis, posterior tuberculum, medial longitudinal fascicle, caudal zone of periventricular hypothalamus, and oculomotor nucleus...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28300633/the-medullary-dorsal-reticular-nucleus-as-a-relay-for-descending-pronociception-induced-by-the-mglur5-in-the-rat-infralimbic-cortex
#2
Ana David-Pereira, Boriss Sagalajev, Hong Wei, Armando Almeida, Antti Pertovaara, Filipa Pinto-Ribeiro
Metabotropic glutamate receptor 5 (mGluR5) activation in the infralimbic cortex (IL) induces pronociceptive behavior in healthy and monoarthritic rats. Here we studied whether the medullary dorsal reticular nucleus (DRt) and the spinal TRPV1 are mediating the IL/mGluR5-induced spinal pronociception and whether the facilitation of pain behavior is correlated with changes in spinal dorsal horn neuron activity. For drug administrations, all animals had a cannula in the IL as well as a cannula in the DRt or an intrathecal catheter...
March 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28295330/in-vitro-characterisation-of-cell-level-neurophysiological-diversity-in-the-rostral-nucleus-reuniens-of-adult-mice
#3
D A Walsh, J T Brown, A D Randall
The nucleus reuniens (Re) is the largest of the midline thalamic nuclei. We have performed a detailed neurophysiological characterization of neurons in the rostral Re of brain slices prepared from adult male mice. At resting potential (-63.7 ± 0.6 mV), circa 90% of Re neurons fired action potentials, typically continuously at ∼8 Hz. Although Re neurons experience a significant spontaneous barrage of fast, amino-acid-mediate synaptic transmission, this was not predominantly responsible for spontaneous spiking as firing persisted in the presence of glutamate and GABA receptor antagonists...
March 11, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28292021/antinociceptive-pharmacological-profile-of-dysphania-graveolens-in-mouse
#4
Myrna Déciga-Campos, Rachel Mata, Isabel Rivero-Cruz
This work evaluates the potential antinociceptive activity of Dysphania graveolens, traditional medicinal plant used in Mexico to treat stomach pain. A CH2Cl2-MeOH extract, infusion and essential oil from aerial parts of Dysphania graveolens were evaluated in hot plate and writhing tests in mice. The metabolites pinostrobin, pinocembrin and chrysin were isolated from the Dysphania graveolens infusion; next, they were evaluated in both nociceptive tests. To confirm the antinociceptive activity and explore the possible participation of opioid, GABA and serotonin receptors in the pharmacological mechanism, a formalin test was used...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28288863/toluene-s-effects-on-activity-and-extracellular-dopamine-in-the-mouse-are-altered-by-gabaa-antagonism
#5
Sean P Callan, Aaron K Apawu, Tiffany A Mathews, Scott E Bowen
The abuse of inhalants like toluene continues to be widespread around the world, especially among children and teenagers. Despite its frequency of misuse, the dynamics between dopamine (DA) and gamma-aminobutyric acid (GABA) in response to toluene exposure remains unclear. To further decipher toluene's actions, we used a dynamic exposure system in combination with microdialysis to examine in vivo the effects of acutely inhaled toluene on DA release within the mouse caudate putamen (CPu). Results show that toluene inhalation produced increases in DA levels and locomotor activity...
March 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28275719/a-negative-allosteric-modulator-for-%C3%AE-5-subunit-containing-gaba-receptors-exerts-a-rapid-and-persistent-antidepressant-like-action-without-the-side-effects-of-the-nmda-receptor-antagonist-ketamine-in-mice
#6
Panos Zanos, Mackenzie E Nelson, Jaclyn N Highland, Samuel R Krimmel, Polymnia Georgiou, Todd D Gould, Scott M Thompson
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28271626/acupuncture-reduces-relapse-to-cocaine-seeking-behavior-via-activation-of-gaba-neurons-in-the-ventral-tegmental-area
#7
Wyju Jin, Min Sun Kim, Eun Young Jang, Jun Yeon Lee, Jin Gyeom Lee, Hong Yu Kim, Seong Shoon Yoon, Bong Hyo Lee, Suchan Chang, Jae Hyo Kim, Kwang H Choi, Ho Koo, Young Seob Gwak, Scott C Steffensen, Yeon-Hee Ryu, Hee Young Kim, Chae Ha Yang
There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior...
March 7, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28267198/serotonergic-transmission-at-merkel-discs-modulation-by-exogenously-applied-chemical-messengers-and-involvement-of-ih-currents
#8
Weipang Chang, Hirosato Kanda, Ryo Ikeda, Jennifer Ling, Jianguo G Gu
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In the present study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28254751/glycinergic-inhibition-of-bat-sympathetic-premotor-neurons-in-rostral-raphe-pallidus
#9
Ellen Paula Santos da Conceição, Christopher J Madden, Shaun F Morrison
The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine if a tonic activation of glycineA receptors (GlyAR) in the rRPa contributes to the inhibitory regulation of BAT SNA and of cardiovascular parameters in anesthetized rats. Nanoinjection of the GlyAR antagonist, strychnine (STR), into the rRPa of intact rats increased BAT sympathetic nerve activity (SNA, peak: +495%), BAT temperature (TBAT, +1.1 ºC), expired CO2, (+0...
March 2, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28230107/regulation-of-visual-wulst-cell-responsiveness-by-imprinting-causes-stimulus-specific-activation-of-rostral-cells
#10
Tomoharu Nakamori, Tomomi Kato, Hiroyuki Sakagami, Kohichi Tanaka, Hiroko Ohki-Hamazaki
Imprinting behaviour in chicks can be induced exclusively during a short period after hatching. During this period, visual information on the imprinting stimulus is conveyed to the visual Wulst (VW) in the telencephalon, which corresponds to the visual cortex of mammals, and then to the memory-storing region known as the intermediate medial mesopallium. These two regions are indispensable for imprinting. We previously showed that imprinting training altered the response pattern of the VW to the imprinting stimulus; however, the precise distribution of cells and the mechanism involved with this altered response remains unclear...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28221080/blockade-of-glutamatergic-transmission-in-the-primate-basolateral-amygdala-suppresses-active-behavior-without-altering-social-interaction
#11
Patrick A Forcelli, Laurie L Wellman, Ludise Malkova
The amygdala is an integrator of affective processing, and a key component of a network regulating social behavior. While decades of lesion studies in nonhuman primates have shown alterations in social interactions after amygdala damage, acute manipulations of the amygdala in primates have been underexplored. We recently reported (Wellman, Forcelli, Aguilar, & Malkova, 2016) that acute pharmacological inhibition of the basolateral complex of the amygdala (BLA) or the central nucleus of the amygdala increased affiliative social interactions in experimental dyads of macaques; this was achieved through microinjection of a GABA-A receptor agonist...
April 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#12
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28176016/choline-induces-opposite-changes-in-pyramidal-neuron-excitability-and-synaptic-transmission-through-a-nicotinic-receptor-independent-process-in-hippocampal-slices
#13
E Albiñana, J G Luengo, A M Baraibar, M D Muñoz, L Gandía, J M Solís, J M Hernández-Guijo
Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats. Choline caused a reversible depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner that was not affected by α7 nAChR antagonists...
February 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28163104/age-dependent-regulation-of-gaba-transmission-by-kappa-opioid-receptors-in-the-basolateral-amygdala-of-sprague-dawley-rats
#14
K R Przybysz, D F Werner, M R Diaz
Anxiety disorders are one of the most common and debilitating mental illnesses worldwide. Growing evidence indicates an age-dependent rise in the incidence of anxiety disorders from adolescence through adulthood, suggestive of underlying neurodevelopmental mechanisms. Kappa opioid receptors (KORs) are known to contribute to the development and expression of anxiety; however, the functional role of KORs in the basolateral amygdala (BLA), a brain structure critical in mediating anxiety, particularly across ontogeny, are unknown...
February 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28161374/chronic-gabaergic-blockade-in-the-spinal-cord-in%C3%A2-vivo-induces-motor-alterations-and-neurodegeneration
#15
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord...
February 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28153485/loop-f-of-the-%C3%AE-subunit-determines-the-pharmacologic-profile-of-novel-competitive-inhibitors-of-gabaa-receptors
#16
Balázs Mihalik, Adrienn Pálvölgyi, Ferenc Bogár, Katalin Megyeri, István Ling, József Barkóczy, Ferenc Bartha, Tamás A Martinek, István Gacsályi, Ferenc A Antoni
The neurotransmitter γ-amino butyric acid (GABA) has a fundamental role in CNS function and ionotropic (GABAA) receptors that mediate many of the actions of GABA are important therapeutic targets. This study reports the mechanism of action of novel GABAA antagonists based on a tricyclic oxazolo-2,3-benzodiazepine scaffold. These compounds are orthosteric antagonists of GABA on heteropentameric GABAA receptors of αxβ2γ2 configuration expressed in HEK293 cells. In silico modelling predicted that the test compounds docked in the GABA binding-pocket and would interact with amino-acid residues in the α- and β-subunit interface that are known to be important for the binding of GABA...
January 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28146602/pharmacological-characterization-of-the-excitatory-cys-loop-gaba-receptor-family-in-c-elegans
#17
Georgina C B Nicholl, Ali K Jawad, Robert Weymouth, Haoming Zhang, Asim A Beg
BACKGROUND AND PURPOSE: Ionotropic GABA receptors are evolutionarily conserved proteins that mediate cellular and network inhibition in both vertebrates and invertebrates. A unique class of excitatory GABA receptors has been identified in several nematode species. Despite well-characterized functions in C. elegans, little is known about the pharmacology of the excitatory GABA receptors EXP-1 and LGC-35. Using a panel of compounds that differentially activate and modulate ionotropic GABA receptors, we investigated the agonist binding site and allosteric modulation of EXP-1 and LGC-35...
February 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28139680/ethanol-dependence-abolishes-monoamine-and-girk-kir3-channel-inhibition-of-orbitofrontal-cortex-excitability
#18
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 naïve mice and in those exposed to chronic intermittent ethanol (CIE) treatment...
January 31, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28123013/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#19
Jasper A Heinsbroek, Daniela N Neuhofer, William C Griffin, Griffin S Siegel, Ana-Clara Bobadilla, Yonatan M Kupchik, Peter W Kalivas
Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28119166/in-vitro-toxicological-evaluation-of-ncs-382-a-high-affinity-antagonist-of-%C3%AE-hydroxybutyrate-ghb-binding
#20
K R Vogel, G R Ainslie, J-B Roullet, A McConnell, K M Gibson
γ-Hydroxybutyric acid (GHB), a minor metabolite of the inhibitory neurotransmitter GABA, can accumulate to significant concentrations in the heritable disorder of GABA degradation, succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD). Moreover, GHB may be employed in therapeutic settings (treatment of narcolepsy), as well as instances of illicit activity, including acquaintance sexual assault and the induction of euphoria. High-affinity binding sites for GHB in the brain have been identified, although the absolute identity of these receptors remains unclear...
January 22, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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