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Gabaa antagonist

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https://www.readbyqxmd.com/read/27924875/gabab-receptor-mediates-opposing-adaptations-of-gaba-release-from-two-types-of-prefrontal-interneurons-after-observational-fear
#1
Lei Liu, Wataru Ito, Alexei Morozov
The observational fear (OF) paradigm in rodents, in which the subject is exposed to a distressed conspecific, elicits contextual fear learning and enhances future passive avoidance learning, which may model certain behavioral traits resulting from traumatic experiences in humans. Because these behaviors affected by the OF, require dorso-medial prefrontal cortex (dmPFC), we searched for synaptic adaptations in dmPFC resulting from OF in mice by recording synaptic responses in dmPFC layer V pyramidal neurons elicited by repeated 5 Hz electrical stimulation of dmPFC layer I, or by optogenetic stimulation of specific interneurons ex vivo one day after OF...
December 7, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27923665/nicotine-enhances-gabaergic-inhibition-of-oxytocin-mrna-expressing-neuron-in-the-hypothalamic-paraventricular-nucleus-in-vitro-in-rats
#2
Ke-Min Zhang, Guo-Yan Zhao, Bin-Bin Zhang, Qi Xu, Chun-Ping Chu, Hua Jin, De-Lai Qiu
We recently found that extracellular administration of nicotine indirectly excited hypothalamic paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) mRNA-expressing neurons. In this study, we studied the effect of nicotine on PVN oxytocin (OT) mRNA-expressing neuron in vitro in rats, by whole-cell patch-clamp recording technique, immunohistochemistry methods and single-cell reverse-transcription multiplex polymerase chain reaction (SC-RT-mPCR) methods Our results showed that 79.3% (73/92) of the 92 PVN putative magnocellular neurons co-expressed GAPDH mRNA and OT mRNA...
December 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27884341/propofol-inhibits-t-helper-cell-type-2-differentiation-by-inducing-apoptosis-via-activating-gamma-aminobutyric-acid-receptor
#3
Jingxia Meng, Xin Xin, Zhen Liu, Hao Li, Bo Huang, Yuguang Huang, Jing Zhao
BACKGROUND: Propofol has been shown to attenuate airway hyperresponsiveness in asthma patients. Our previous study showed that it may alleviate lung inflammation in a mouse model of asthma. Given the critical role of T-helper cell type-2 (Th2) differentiation in asthma pathology and the immunomodulatory role of the gamma-aminobutyric acid type A (GABAA) receptor, we hypothesized that propofol could alleviate asthma inflammation by inhibiting Th2 cell differentiation via the GABA receptor...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27865151/effects-of-the-benzodiazepine-gabaa-%C3%AE-1-preferring-antagonist-3-isopropoxy-%C3%AE-carboline-hydrochloride-3-isopbc-on-alcohol-seeking-and-self-administration-in-baboons
#4
August F Holtyn, V V N Phani Babu Tiruveedhula, Michael Rajesh Stephen, James M Cook, Elise M Weerts
BACKGROUND: The major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), modulates many of the behavioral effects of alcohol, including sedation, tolerance, and withdrawal. The α1 subunit of the benzodiazepine GABAA receptor is the most widely expressed alpha subunit in the brain, and has been implicated in the reinforcing- and abuse-related effects of alcohol. The aim of the present study was to examine whether treatment with a benzodiazepine GABAA α1-preferring ligand, 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC), selectively decreases alcohol seeking and consumption...
November 4, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#5
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27818352/exercise-combined-with-low-level-gabaa-receptor-inhibition-up-regulates-the-expression-of-neurotrophins-in-the-motor-cortex
#6
Kazuma Takahashi, Hiroshi Maejima, Gaku Ikuta, Hiroki Mani, Tadayoshi Asaka
Neurotrophins play a crucial role in neuroplasticity, neurogenesis, and neuroprotection in the central nervous system. Aerobic exercise is known to increase the expression of BDNF in the cerebral cortex. Several animal studies have evaluated the tonic inhibition of GABAergic synapses to enhance hippocampal plasticity as well as learning and memory, whereas the effects of GABAergic inhibition on plasticity in the cerebral cortex related to motor learning are not well characterized. The objective of the present study was to examine the interactive effect of low-level GABAA receptor inhibition and exercise on the expression of neurotrophins including BDNF in the murine motor cortex...
January 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27780724/bicuculline-a-gabaa-receptor-antagonist-blocked-hpa-axis-activation-induced-by-ghrelin-under-an-acute-stress
#7
M S Gastón, M P Cid, N A Salvatierra
Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABAA receptor competitive antagonist) but not by diazepam (a GABAA receptor allosteric agonist) in neonatal meat-type chicks (Cobb)...
October 22, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27778437/increase-of-kcc2-in-hippocampal-synaptic-plasticity-disturbances-after-perinatal-ethanol-exposure
#8
Benoît Silvestre de Ferron, Catherine Vilpoux, Myriam Kervern, Alexandre Robert, Johan Antol, Mickael Naassila, Olivier Pierrefiche
Low to moderate perinatal ethanol exposure (PEE) may have disastrous consequences for the central nervous system resulting notably in permanent cognitive deficits. Learning and memory are mediated in the hippocampus by long-term potentiation (LTP) and long term depression (LTD), two forms of synaptic plasticity. PEE decreases LTP but also abnormally facilitates LTD (Kervern et al. ) through a presently unknown mechanism. We studied in rat hippocampus slice, the involvement of the chloride co-transporters NKCC1 and KCC2, in the role of GABAA inhibitions in facilitated LTD after moderate PEE...
October 25, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27764759/6-methoxyflavanone-attenuates-mechanical-allodynia-and-vulvodynia-in-the-streptozotocin-induced-diabetic-neuropathic-pain
#9
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27757785/2-3-o-substituted-atp-derivatives-as-potent-antagonists-of-purinergic-p2x3-receptors-and-potential-analgesic-agents
#10
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27747877/behavioral-pharmacology-of-the-odor-span-task-effects-of-flunitrazepam-ketamine-methamphetamine-and-methylphenidate
#11
Mark Galizio, Brooke April, Melissa Deal, Andrew Hawkey, Danielle Panoz-Brown, Ashley Prichard, Katherine Bruce
The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task...
November 2016: Journal of the Experimental Analysis of Behavior
https://www.readbyqxmd.com/read/27746347/propofol-induced-spike-firing-suppression-is-more-pronounced-in-pyramidal-neurons-than-in-fast-spiking-neurons-in-the-rat-insular-cortex
#12
Keisuke Kaneko, Yuko Koyanagi, Yoshiyuki Oi, Masayuki Kobayashi
Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates inward current (Ih), K(+), and voltage-gated Na(+) currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27732892/decreasing-gaba-function-within-the-medial-prefrontal-cortex-or-basolateral-amygdala-decreases-sociability
#13
Tracie A Paine, Nathan Swedlow, Lucien Swetschinski
INTRODUCTION: Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. METHODS: Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0...
January 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27729478/contribution-of-gabaa-glycine-and-opioid-receptors-to-sacral-neuromodulation-of-bladder-overactivity-in-cats
#14
Xuewen Jiang, Thomas W Fuller, Jathin Bandari, Utsav Bansal, Zhaocun Zhang, Bing Shen, Jicheng Wang, James R Roppolo, William C de Groat, Changfeng Tai
In α-chloralose anesthetized cats, we examined the role GABAA, glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (p<0.01) reduced bladder capacity to 59.5±4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (p<0.01) increased bladder capacity to 105.3±9.0% and 134...
October 11, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27725215/additive-effect-of-harmane-and-muscimol-for-memory-consolidation-impairment-in-inhibitory-avoidance-task
#15
Mohammad Nasehi, Parastoo Morteza-Zadeh, Fatemeh Khakpai, Mohammad-Reza Zarrindast
In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABAA receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABAA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABAA receptor agonist - impaired memory consolidation...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27717879/unravelling-cortico-hypothalamic-pathways-regulating-unconditioned-fear-induced-antinociception-and-defensive-behaviours
#16
Luiz Luciano Falconi-Sobrinho, Tayllon Dos Anjos-Garcia, Daoud Hibrahim Elias-Filho, Norberto Cysne Coimbra
The medial prefrontal cortex can influence unconditioned fear-induced defensive mechanisms organised by diencephalic neurons that are under tonic GABAergic inhibition. The posterior hypothalamus (PH) is involved with anxiety- and panic attack-like responses. To understand this cortical mediation, our study characterised anterior cingulate cortex (ACC)-PH pathways and investigated the effect of ACC local inactivation with lidocaine. We also investigated the involvement of PH ionotropic glutamate receptors in the defensive behaviours and fear-induced antinociception by microinjecting NBQX (an AMPA/kainate receptor antagonist) and LY235959 (a NMDA receptor antagonist) into the PH...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27714629/discriminative-stimulus-effects-of-abused-inhalants
#17
Keith L Shelton
Inhalants are a loosely organized category of abused compounds defined entirely by their common route of administration. Inhalants include volatile solvents, fuels, volatile anesthetics, gasses, and liquefied refrigerants, among others. They are ubiquitous in modern society as ingredients in a wide variety of household, commercial, and medical products. Persons of all ages abuse inhalants but the highest prevalence of abuse is in younger adolescents. Although inhalants have been shown to act upon a host of neurotransmitter receptors, the stimulus effects of the few inhalants which have been trained or tested in drug discrimination procedures suggest that their discriminative stimulus properties are mediated by a few key neurotransmitter receptor systems...
October 7, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27678415/ethanol-potentiates-both-gabaergic-and-glutamatergic-signaling-in-the-lateral-habenula
#18
Wanhong Zuo, Liwei Wang, Lixin Chen, Krešimir Krnjević, Rao Fu, Xia Feng, Wen He, Seungwoo Kang, Avi Shah, Alex Bekker, Jiang-Hong Ye
Ethanol's aversive property may limit it's use, but the underlying mechanisms are no well-understood. Emerging evidence suggests a critical role for the lateral habenula (LHb) in the aversive response to various drugs, including ethanol. We previously showed that ethanol enhances glutamatergic transmission and stimulates LHb neurons. GABAergic transmission, a major target of ethanol in many brain regions, also tightly regulates LHb activity. This study assessed the action of ethanol on LHb GABAergic transmission in rat brain slices...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27672659/antihyperalgesic-effect-of-hesperidin-improves-with-diosmin-in-experimental-neuropathic-pain
#19
Azucena I Carballo-Villalobos, María-Eva González-Trujano, Francisco Pellicer, Francisco J López-Muñoz
Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27668426/modulating-behavior-in-c-elegans-using-electroshock-and-antiepileptic-drugs
#20
Monica G Risley, Stephanie P Kelly, Kailiang Jia, Brock Grill, Ken Dawson-Scully
The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C...
2016: PloS One
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