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https://www.readbyqxmd.com/read/28931433/role-of-gabaa-receptors-in-alcohol-use-disorders-suggested-by-chronic-intermittent-ethanol-cie-rodent-model
#1
REVIEW
Richard W Olsen, Jing Liang
GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. One-dose ethanol exposure induces transient plastic changes in GABAA receptor subunit levels, composition, and regional and subcellular localization. Rapid down-regulation of early responder δ subunit-containing GABAA receptor subtypes mediating ethanol-sensitive tonic inhibitory currents in critical neuronal circuits corresponds to rapid tolerance to ethanol's behavioral responses. Slightly slower, α1 subunit-containing GABAA receptor subtypes mediating ethanol-insensitive synaptic inhibition are down-regulated, corresponding to tolerance to additional ethanol behaviors plus cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids, especially sedative-hypnotic effects...
September 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28929924/the-search-for-a-subtype-selective-pet-imaging-agent-for-the-gabaa-receptor-complex-evaluation-of-the-radiotracer-11-c-ado-in-nonhuman-primates
#2
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA, GABAB, and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28928398/bumetanide-treatment-during-early-development-rescues-maternal-separation-induced-susceptibility-to-stress
#3
Die Hu, Zhou-Long Yu, Yan Zhang, Ying Han, Wen Zhang, Lin Lu, Jie Shi
Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na(+)/K(+)/2Cl(-) cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K(+)/2Cl(-) cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABAA) receptor subunits on postnatal day 40 in the hippocampus...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927958/defective-gabaergic-neurotransmission-in-the-nucleus-tractus-solitarius-in-mecp2-null-mice-a-model-of-rett-syndrome
#4
Chao-Yin Chen, Jacopo Di Lucente, Yen-Chu Lin, Cheng-Chang Lien, Michael A Rogawski, Izumi Maezawa, Lee-Way Jin
Rett syndrome (RTT) is a devastating neurodevelopmental disorder caused by loss-of-function mutations in the X-linked methyl-CpG binding protein 2 (Mecp2) gene. GABAergic dysfunction has been implicated contributing to the respiratory dysfunction, one major clinical feature of RTT. The nucleus tractus solitarius (NTS) is the first central site integrating respiratory sensory information that can change the nature of the reflex output. We hypothesized that deficiency in Mecp2 gene reduces GABAergic neurotransmission in the NTS...
September 16, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28923348/stimulation-of-accumbal-gabaa-receptors-inhibits-delta2-but-not-delta1-opioid-receptor-mediated-dopamine-efflux-in-the-nucleus-accumbens-of-freely-moving-rats
#5
Yuri Aono, Yuri Kiguchi, Yuriko Watanabe, John L Waddington, Tadashi Saigusa
The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABAA receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABAA receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABAA receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28921686/the-effects-of-dynamical-synapses-on-firing-rate-activity-a-spiking-neural-network-model
#6
Radwa Khalil, Marie Z Moftah, Ahmed A Moustafa
Accumulating evidence relates the fine-tuning of synaptic maturation and regulation of neural network activity to several key factors, including GABAA signaling and a lateral spread length between neighboring neurons (i.e. local connectivity). Furthermore, a number of studies consider Short-Term synaptic Plasticity (STP) as an essential element in the instant modification of synaptic efficacy in the neuronal network and in modulating responses to sustained ranges of external Poisson Input Frequency (IF). Nevertheless, evaluating the firing activity in response to the dynamical interaction between STP (triggered by ranges of IF), and these key parameters in vitro remains elusive...
September 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28919062/progress-and-challenges-in-anti-obesity-pharmacotherapy
#7
REVIEW
Daniel H Bessesen, Luc F Van Gaal
Obesity is a serious and growing worldwide health challenge. Healthy lifestyle choices are the foundation of obesity treatment. However, weight loss can lead to physiological adaptations that promote weight regain. As a result, lifestyle treatment alone typically produces only modest weight loss that is difficult to sustain. In other metabolic diseases, pharmacotherapy is an accepted adjunct to lifestyle. Several anti-obesity drugs have been approved in the USA, European Union, Australia, and Japan including sympathomimetics, pancreatic lipase inhibitors, GABAA receptor activators, a serotonin 2C receptor agonist, opioid antagonist, dopamine-norepinephrine reuptake inhibitor, and glucagon-like peptide-1 (GLP-1) receptor agonists...
September 14, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28917695/the-impact-of-gabaergic-drugs-on-tms-induced-brain-oscillations-in-human-motor-cortex
#8
Isabella Premoli, Til O Bergmann, Matteo Fecchio, Mario Rosanova, Andrea Biondi, Paolo Belardinelli, Ulf Ziemann
Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30-200 ms after TMS) synchronization in the α- and β-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200-400 ms) α- and β-desynchronization over the stimulated and contralateral sensorimotor cortex...
September 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/28916137/oxytocin-induces-penile-erection-and-yawning-when-injected-into-the-bed-nucleus-of-the-stria-terminalis-involvement-of-glutamic-acid-dopamine-and-nitric-oxide
#9
Fabrizio Sanna, Jessica Bratzu, Antonio Argiolas, Maria Rosaria Melis
Oxytocin (5-100ng), but not Arg(8)-vasopressin (100ng), injected unilaterally into the bed nucleus of the stria terminalis (BNST) induces penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished not only by the oxytocin receptor antagonist d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1μg), but also by (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin...
September 18, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28913780/anxiolytic-like-effects-of-%C3%AE-asarone-in-a-mouse-model-of-chronic-pain
#10
Jiao Tian, Zhen Tian, Shu-Li Qin, Pu-Yu Zhao, Xun Jiang, Zhen Tian
α-asarone (ASR) is a major bioactive compound isolated from the rhizome of Acorus tatarinowii Schott and it has extensive biological effects. Clinically, anxiety disorder is a common comorbidity of chronic pain. However, limited information is available regarding the effects of ASR on chronic pain-related anxiety. This study aims to evaluate the anxiolytic effects of ASR in chronic pain mice. Chronic inflammatory pain was induced by hind-paw injection of complete Freund's adjuvant (CFA). Behavioral tests, western-blot analysis and whole-cell patch recordings were performed to evaluate the subsequent events...
September 15, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28905487/endogenous-neurosteroids-influence-synaptic-gabaa-receptors-during-post-natal-development
#11
REVIEW
Delia Belelli, Adam R Brown, Scott J Mitchell, Ben G Gunn, Murray B Herd, Grant Phillips, Mohsen Seifi, Jerome D Swinny, Jeremy J Lambert
GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity, to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurons to appropriately influence the window for postsynaptic excitation...
September 14, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28905384/heteromeric-%C3%AE-%C3%AE-%C3%A2-glycine-receptors-regulate-excitability-in-parvalbumin-expressing-dorsal-horn-neurons-through-phasic-and-tonic-glycinergic-inhibition
#12
M A Gradwell, K A Boyle, R J Callister, D I Hughes, B A Graham
The dorsal horn (DH) of the spinal cord is an important site for modality specific processing of sensory information and is essential for contextually relevant sensory experience. Parvalbumin-expressing inhibitory interneurons (PV + INs) have functional properties and connectivity that enables them to segregate tactile and nociceptive information. Here we examine inhibitory drive to PV + INs using targeted patch-clamp recording in spinal cord slices from adult transgenic mice that express enhanced green fluorescent protein in PV + INs...
September 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28901728/gaba-type-a-receptor-trafficking-and-the-architecture-of-synaptic-inhibition
#13
REVIEW
Joshua M Lorenz-Guertin, Tija C Jacob
Ubiquitous expression of GABA type A receptors (GABAA R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABAA Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition...
September 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28901722/%C3%AE-6-subunit-containing-nicotinic-receptors-mediate-low-dose-ethanol-effects-on-ventral-tegmental-area-neurons-and-ethanol-reward
#14
Scott C Steffensen, Samuel I Shin, Ashley C Nelson, Stephanie S Pistorius, Stephanie B Williams, Taylor J Woodward, Hyun Jung Park, Lindsey Friend, Ming Gao, Fenfei Gao, Devin H Taylor, M Foster Olive, Jeffrey G Edwards, Sterling N Sudweeks, Lori M Buhlman, J Michael McIntosh, Jie Wu
Dopamine (DA) neuron excitability is regulated by inhibitory GABAergic synaptic transmission and modulated by nicotinic acetylcholine receptors (nAChRs). The aim of this study was to evaluate the role of α6 subunit-containing nAChRs (α6*-nAChRs) in acute ethanol effects on ventral tegmental area (VTA) GABA and DA neurons. α6*-nAChRs were visualized on GABA terminals on VTA GABA neurons, and α6*-nAChR transcripts were expressed in most DA neurons, but only a minority of VTA GABA neurons from GAD67 GFP mice...
September 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28900387/social-isolation-in-early-versus-late-adolescent-mice-is-associated-with-persistent-behavioral-deficits-that-can-be-improved-by-neurosteroid-based-treatment
#15
Andrea Locci, Philippe Geoffroy, Michel Miesch, Ayikoe-Guy Mensah-Nyagan, Graziano Pinna
Early trauma and stress exposure during a critical period of life may increase the risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in adulthood. The first-choice treatment for MDD and PTSD are selective serotonin reuptake inhibitor (SSRI) antidepressants. Unfortunately, half of MDD and PTSD patients show resistance to the therapeutic effects of these drugs and more efficient treatments are essential. Both MDD and PTSD patients present reduced levels of allopregnanolone (Allo), a potent endogenous positive allosteric modulator of GABA action at GABAA receptors which are normalized by SSRIs in treatment responders...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28900286/adolescent-thc-exposure-causes-enduring-prefrontal-cortical-disruption-of-gabaergic-inhibition-and-dysregulation-of-sub-cortical-dopamine-function
#16
Justine Renard, Hanna J Szkudlarek, Cecilia P Kramar, Christina E L Jobson, Kyra Moura, Walter J Rushlow, Steven R Laviolette
Chronic adolescent marijuana use has been linked to the later development of psychiatric diseases such as schizophrenia. GABAergic hypofunction in the prefrontal cortex (PFC) is a cardinal pathological feature of schizophrenia and may be a mechanism by which the PFC loses its ability to regulate sub-cortical dopamine (DA) resulting in schizophrenia-like neuropsychopathology. In the present study, we exposed adolescent rats to Δ-9-tetra-hydrocannabinol (THC), the psychoactive component in marijuana. At adulthood, we characterized the functionality of PFC GABAergic neurotransmission and its regulation of sub-cortical DA function using molecular, behavioral and in-vivo electrophysiological analyses...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28895076/new-botanical-anxiolytics-for-use-in-companion-animals-and-humans
#17
Rui Liu, Fida Ahmed, Christian Cayer, Martha Mullally, Ana Francis Carballo, Marco Otarola Rojas, Mario Garcia, John Baker, Aleksandar Masic, Pablo E Sanchez, Luis Poveda, Zul Merali, Tony Durst, John T Arnason
As part of our ongoing research into botanical therapies for anxiety disorders, the neotropical vine Souroubea sympetala was chosen for study as a phytochemical discovery strategy focusing on rare Central American plant families. When orally administered to male Sprague-Dawley rats, the crude plant extract, its ethyl acetate fraction, supercritical carbon dioxide fraction, or its isolated triterpenes reduced anxiety and/or fear-related behavior in standardized behavioral models. Pharmacological studies showed that the extracts acted at the benzodiazepine GABAA receptor and reduced corticosterone levels...
September 11, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28894409/the-effect-of-4-hydroxybenzaldehyde-on-the-%C3%AE-aminobutyric-acid-type-a-receptor
#18
COMMENT
Jingli Zhang, Habsah Mohamad, Jia Hui Wong, Muhammad Bilal, Abdul Hadi Bin Ismail, Amelia Jane Lloyd, Abdul Aziz Mohamed Yusoff, Hasnah Osman, Kok Tong Wong, Zamzuri Idris, Jafri Malin Abdullah
The α1β2γ2 subtype of GABAA receptors is the most commonly found GABAA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a α1β2γ2S/L subtype for application as an in vitro model for the screening of compounds that modulate receptor activities. In fact, 4-hydroxybenzaldehyde (4-HB) has been identified as one of the major components in Dendrocalamus asper bamboo shoots in our previous study, and the current study showed that at 101.7 μM, 4-HB significantly reduced the GABA-induced chloride current of GABAA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations...
March 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28893667/amnestic-drugs-in-the-odor-span-task-effects-of-flunitrazepam-zolpidem-and-scopolamine
#19
Mark Galizio, Michael Mathews, Madeleine Mason, Danielle Panoz-Brown, Ashley Prichard, Paul Soto
The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABAA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination...
September 8, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28893591/neurosteroid-dehydroepiandrosterone-improves-active-avoidance-retrieval-and-induces-antidepressant-like-behavior-in-rats
#20
Janko Samardzic, Boris Hencic, Jasna Jancic, Dragana Jadzic, Milos Djuric, Dragan I Obradovic, Dubravka Svob Strac
Various studies reported beneficial effects of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), the neurosteroids involved in various brain functions, on synaptic plasticity, neuronal survival, memory, learning and behavior. This study aimed to investigate the behavioral profile of acute DHEA treatment by using active avoidance (AA) task, primarily predictive of the effects on the retrieval-based learning, and by applying forced swim test (FST), for assessment of antidepressant-like potential. Adult male Wistar rats received intraperitoneal injections of either DHEA (2, 10, 20mg/kg) or solvent, 30min prior to testing...
September 8, 2017: Neuroscience Letters
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