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Gaba a antagonist

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https://www.readbyqxmd.com/read/28104530/long-lasting-alterations-of-hippocampal-gabaergic-neurotransmission-in-adult-rats-following-perinatal-%C3%AE-9-thc-exposure
#1
Sarah Beggiato, Andrea Celeste Borelli, Maria Cristina Tomasini, Lucia Morgano, Tiziana Antonelli, Sergio Tanganelli, Vincenzo Cuomo, Luca Ferraro
The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored...
January 16, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28100744/compensatory-activation-of-cannabinoid-cb2-receptor-inhibition-of-gaba-release-in-the-rostral-ventromedial-medulla-in-inflammatory-pain
#2
Ming-Hua Li, Katherine L Suchland, Susan L Ingram
: The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM, but it is not known whether this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature IPSCs (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared with naive rats...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28098344/inhibition-of-oxytocin-and-vasopressin-neuron-activity-in-rat-hypothalamic-paraventricular-nucleus-by-relaxin-3-rxfp3-signalling
#3
Alan Kania, Anna Czerw, Agnieszka Grabowiecka, Camila de Ávila, Tomasz Blasiak, Zenon Rajfur, Marian H Lewandowski, Grzegorz Hess, Elena Timofeeva, Andrew L Gundlach, Anna Blasiak
KEY-POINTS: Relaxin-3 is a stress-responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated a direct, RXFP3-dependent, inhibitory action of relaxin-3 on oxytocin and vasopressin PVN neuron electrical activity, a putative cellular mechanism of orexinergic actions of relaxin-3. We observed a Gαi/o -protein-dependent inhibitory influence of selective RXFP3 activation on PVN neuronal activity in vitro and demonstrated a direct action of RXFP3 activation on oxytocin and vasopressin PVN neurons, confirmed by their abundant expression of RXFP3 mRNA...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28087766/control-of-amygdala-circuits-by-5-ht-neurons-via-5-ht-and-glutamate-co-transmission
#4
Ayesha Sengupta, Marco Bocchio, David M Bannerman, Trevor Sharp, Marco Capogna
: The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Thus, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin (ChR2) genetically targeted to 5-HT neurons...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28071892/transient-adenosine-release-is-modulated-by-nmda-and-gabab-receptors
#5
Michael D Nguyen, Ying Wang, Mallikarjunarao Ganesana, B Jill Venton
Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1 and A2a receptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen...
January 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28066142/participation-of-central-gabaa-receptors-in-the-trigeminal-processing-of-mechanical-allodynia-in-rats
#6
Min Ji Kim, Young Hong Park, Kui Ye Yang, Jin Sook Ju, Yong Chul Bae, Seong Kyu Han, Dong Kuk Ahn
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28057450/antiepileptic-drugs-prevent-seizures-in-hyperbaric-oxygen-a-novel-model-of-epileptiform-activity
#7
Ivan T Demchenko, Sergei Yu Zhilyaev, Alexander N Moskvin, Alexander I Krivchenko, Claude A Piantadosi, Barry W Allen
Breathing oxygen at sufficiently elevated pressures can trigger epileptiform seizures. Therefore, we tested the hypothesis that pre-treatment with FDA-approved antiepileptic drugs could prevent seizure onset in hyperoxia at 5 atmospheres absolute. We selected drugs from two putative functional categories, Na(+)-channel antagonists and GABA enhancers, each administered intraperitoneally at four doses in separate groups of C57BL/6 mice. The drugs varied in efficacy at the doses used. Of the five tested Na(+)-channel antagonists, carbamazepine and lamotrigine more than tripled seizure latency compared to values seen in vehicle controls...
January 2, 2017: Brain Research
https://www.readbyqxmd.com/read/28038985/exploring-the-mechanism-by-which-accumbal-deep-brain-stimulation-attenuates-morphine-induced-reinstatement-through-manganese-enhanced-mri-and-pharmacological-intervention
#8
Lei Zhang, Ying Cui, Ying-Chun Wang, Hong Yin, Jian-Min Zheng, Lu Huang, Zhen-Wei Zhao, Jiang Li
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has been applied to attenuate drug relapses in animal studies and clinical treatments. However, the mechanisms by which DBS produces its therapeutic effects remain largely unknown. This study is the first to combine manganese-enhanced magnetic resonance imaging (MRI) with DBS to explore the effects of accumbal DBS on the relapse pathway of rats. The images suggested that DBS produced an antidromic activation of the cortico-accumbal afferents. To verify the activating effects of DBS, the expression levels of the protein encoded by the immediate early gene c-Fos following DBS were measured using immunochemical methods...
December 27, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28025973/lateral-habenula-involvement-in-impulsive-cocaine-seeking
#9
Agustin Zapata, Eun-Kyung Hwang, Carl R Lupica
The lateral habenula (LHb) is a brain structure receiving inputs from limbic forebrain areas and innervating major midbrain monoaminergic nuclei. Evidence indicates LHb involvement in sleep control, reward-based decision making, avoidance of punishment, and responses to stress. Additional work has established that the LHb mediates negative feedback in response to aversive events. As a hallmark of drug addiction is the inability to limit drug use despite negative consequences, we hypothesize that LHb dysfunction may have a role in the lack of control over drug seeking...
January 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28011073/behavioral-effects-and-neuroanatomical-targets-of-acute-atrazine-exposure-in-the-male-sprague-dawley-rat
#10
V M Rodriguez, M S Mendoza-Trejo, I Hernandez-Plata, M Giordano
Atrazine (ATR) is an herbicide broadly used in the world to control weeds in corn and sorghum fields, and it is potentially toxic for the dopaminergic system. Alterations in dopaminergic markers after ATR administration in rats and C57BL/6 mice have been reported. Behaviorally, it has been observed that ATR exposure causes hypoactivity shortly after its administration. To understand how acute ATR administration induces hypoactivity, we set out to map the brain areas responsive to ATR using c-Fos as a marker of neuronal activity, and tyrosine hydroxylase (TH) as a marker of dopaminergic neurons...
December 21, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27986929/genetic-and-pharmacologic-manipulation-of-tlr4-has-minimal-impact-on-ethanol-consumption-in-rodents
#11
R Adron Harris, Michal Bajo, Richard L Bell, Yuri A Blednov, Florence P Varodayan, Jay Truitt, Giordano de Guglielmo, Amy W Lasek, Marian L Logrip, Leandro F Vendruscolo, Amanda J Roberts, Edward Roberts, Olivier George, Jody Mayfield, Timothy R Billiar, David J Hackam, R Dayne Mayfield, George F Koob, Marisa Roberto, Gregg E Homanics
: Toll-like receptor 4 (TLR4) is a critical component of innate immune signaling and has been implicated in alcohol responses in preclinical and clinical models. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium tested the hypothesis that TLR4 mediates excessive ethanol drinking using i) Tlr4 knockout (KO) rats, ii) selective knockdown of Tlr4 mRNA in mouse nucleus accumbens (NAc), and iii) injection of the TLR4 antagonist (+)-naloxone in mice...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27986928/presynaptic-neuronal-pentraxin-receptor-organizes-excitatory-and-inhibitory-synapses
#12
Sung-Jin Lee, Mengping Wei, Chen Zhang, Stephan Maxeiner, ChangHui Pak, Salome Calado Botelho, Justin Trotter, Fredrik H Sterky, Thomas C Südhof
: Three neuronal pentraxins are expressed in brain, the membrane-bound 'neuronal pentraxin receptor' (NPR) and the secreted proteins NP1 and NARP (a.k.a. NP2). Neuronal pentraxins bind to AMPA-receptors at excitatory synapses, and play important, well-documented roles in the activity-dependent regulation of neural circuits via this binding activity. However, it is unknown whether neuronal pentraxins perform roles in synapses beyond modulating postsynaptic AMPA-receptor-dependent plasticity, and whether they may even act in inhibitory synapses...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27984263/ketamine-increases-the-function-of-%C3%AE-aminobutyric-acid-type-a-receptors-in-hippocampal-and-cortical-neurons
#13
Dian-Shi Wang, Antonello Penna, Beverley A Orser
BACKGROUND: The "dissociative " general anesthetic ketamine is a well-known N-methyl-D-aspartate receptor antagonist. However, whether ketamine, at clinically relevant concentrations, increases the activity of inhibitory γ-aminobutyric acid (GABA) receptor type A (GABAA) receptors in different brain regions remains controversial. Here, the authors studied the effects of ketamine on synaptic and extrasynaptic GABAA receptors in hippocampal neurons. Ketamine modulation of extrasynaptic GABAA receptors in cortical neurons was also examined...
December 14, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27976722/ventral-tegmental-area-glutamate-neurons-co-release-gaba-and-promote-positive-reinforcement
#14
Ji Hoon Yoo, Vivien Zell, Navarre Gutierrez-Reed, Johnathan Wu, Reed Ressler, Mohammad Ali Shenasa, Alexander B Johnson, Kathryn H Fife, Lauren Faget, Thomas S Hnasko
In addition to dopamine neurons, the ventral tegmental area (VTA) contains GABA-, glutamate- and co-releasing neurons, and recent reports suggest a complex role for the glutamate neurons in behavioural reinforcement. We report that optogenetic stimulation of VTA glutamate neurons or terminals serves as a positive reinforcer on operant behavioural assays. Mice display marked preference for brief over sustained VTA glutamate neuron stimulation resulting in behavioural responses that are notably distinct from dopamine neuron stimulation and resistant to dopamine receptor antagonists...
December 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27940994/compensatory-activation-of-cannabinoid-cb2-receptor-inhibition-of-gaba-release-in-the-rostral-ventromedial-medulla-rvm-in-inflammatory-pain
#15
Ming-Hua Li, Katherine L Suchland, Susan L Ingram
: The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM but it is not known if this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared to naïve rats...
December 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27940054/betaine-attenuates-memory-impairment-after-water-immersion-restraint-stress-and-is-regulated-by-the-gabaergic-neuronal-system-in-the-hippocampus
#16
Kazuo Kunisawa, Kiwamu Kido, Natsuki Nakashima, Takuya Matsukura, Toshitaka Nabeshima, Masayuki Hiramatsu
GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05-2090. In this study, we investigated whether memory amelioration by betaine was mediated by the GABAergic neuronal system. Adult male mice were co-administered betaine and GABA receptor antagonists after WIRS...
December 7, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27927951/effects-of-the-selective-%C3%AE-5-gabaar-antagonist-s44819-on-excitability-in-the-human-brain-a-tms-emg-and-tms-eeg-phase-i-study
#17
Ghazaleh Darmani, Carl M Zipser, Gabriele M Böhmer, Karine Deschet, Florian Müller-Dahlhaus, Paolo Belardinelli, Matthias Schwab, Ulf Ziemann
: Alpha-5 gamma-aminobutyric acid type A receptors (α5-GABAARs) are located extrasynaptically, regulate neuronal excitability through tonic inhibition, and are fundamentally important for processes such as plasticity and learning. For example, pharmacological blockade of α5-GABAAR in mice with ischemic stroke improved recovery of function by normalizing exaggerated perilesional α5-GABAAR-dependent tonic inhibition. S44819 is a novel competitive selective antagonist of the α5-GABAAR at the GABA-binding site...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27924875/gabab-receptor-mediates-opposing-adaptations-of-gaba-release-from-two-types-of-prefrontal-interneurons-after-observational-fear
#18
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
#19
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 5, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27910251/cloaked-caged-compounds-chemical-probes-for-two-photon-optoneurobiology
#20
Matthew T Richers, Joseph M Amatrudo, Jeremy P Olson, Graham C R Ellis-Davies
Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a "cloaking" technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time...
January 2, 2017: Angewandte Chemie
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