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https://www.readbyqxmd.com/read/28936791/nmda-receptors-and-no-cgmp-signaling-pathway-mediate-the-diazepam-induced-sensitization-to-withdrawal-signs-in-mice
#1
Sylwia Talarek, Joanna Listos, Jolanta Orzelska-Gorka, Anna Serefko, Jolanta Kotlińska
The goal of the present study was to examine the effects of N-methyl-aspartate (NMDA) receptor antagonists-memantine and ketamine and the drugs modifying the NO:cGMP pathway-NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), the endogenous precursor of NO-L-arginine, and the guanylyl cyclase inhibitor-methylene blue (MB) on the development of sensitization to withdrawal signs precipitated after chronic, interrupted treatment with diazepam, a benzodiazepine receptor agonist, in mice. To develop the sensitization, the mice were divided into groups: continuously and sporadically (with two diazepam-free periods) treated with diazepam (15 mg/kg, sc)...
September 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28922504/selective-remodeling-of-glutamatergic-transmission-to-striatal-cholinergic-interneurons-after-dopamine-depletion
#2
Jose de Jesus Aceves Buendia, Lior Tiroshi, Wei-Hua Chiu, Joshua A Goldberg
The widely-held view that the pathophysiology of Parkinson's disease arises from an under-activation of the direct pathway striatal spiny neurons (dSPNs) has gained support from a recently described weakening of the glutamatergic projection from the parafascicular nucleus (PfN) to dSPNs in experimental parkinsonism. However, the impact of the remodeling of the thalamostriatal projection cannot be fully appreciated without considering its impact on cholinergic interneurons (ChIs) that themselves preferentially activate indirect pathway spiny neurons (iSPNs)...
September 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28921744/cholinergic-basal-forebrain-structures-are-not-essential-for-mediation-of-the-arousing-action-of-glutamate
#3
Zoltán Lelkes, Shamsiiat Abdurakhmanova, Tarja Porkka-Heiskanen
The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin...
September 18, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28912557/a-nmda-receptor-calcium-influx-assay-sensitive-to-stimulation-by-glutamate-and-glycine-d-serine
#4
Hongqiu Guo, L Miguel Camargo, Fred Yeboah, Mary Ellen Digan, Honglin Niu, Yue Pan, Stephan Reiling, Gilberto Soler-Llavina, Wilhelm A Weihofen, Hao-Ran Wang, Y Gopi Shanker, Travis Stams, Anke Bill
N-methyl-D-aspartate-receptors (NMDARs) are ionotropic glutamate receptors that function in synaptic transmission, plasticity and cognition. Malfunction of NMDARs has been implicated in a variety of nervous system disorders, making them attractive therapeutic targets. Overexpression of functional NMDAR in non-neuronal cells results in cell death by excitotoxicity, hindering the development of cell-based assays for NMDAR drug discovery. Here we report a plate-based, high-throughput approach to study NMDAR function...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28901278/neuroinflammation-and-the-immune-kynurenine-pathway-in-anxiety-disorders
#5
Yong-Ku Kim, Sang Won Jeon
BACKGROUND: Recently, neuroinflammation and the immune-kynurenine pathway have received increased attention in the psychoimmunology field of major depressive disorder (MDD), while studies related to anxiety disorders have been very limited. OBJECTIVE: This study reviewed possible mechanisms by which stress or inflammation modulate anxiety through tryptophan metabolism and the kynurenine pathway. METHOD: Relevant literature was identified through a search of MEDLINE via PubMed...
September 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28864281/interaction-of-brain-derived-neurotrophic-factor-val66met-genotype-and-history-of-stress-in-regulation-of-prepulse-inhibition-in-mice
#6
Maarten van den Buuse, John Juan Wen Lee, Emily J Jaehne
The Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism results in reduced activity-dependent BDNF release and has been implicated in schizophrenia. However, effects of the polymorphism on functional dopaminergic and N-methyl-d-aspartate (NMDA) receptor-associated activity remain unclear. We used prepulse inhibition, a measure of sensorimotor gating which is disrupted in schizophrenia, and assessed the effects of acute treatment with the dopamine receptor agonist, apomorphine (APO), and the NMDA receptor antagonist, MK-801...
August 29, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28861501/palmitoylethanolamide-modulates-gpr55-receptor-signaling-in-the-ventral-hippocampus-to-regulate-mesolimbic-dopamine-activity-social-interaction-and-memory-processing
#7
Cecilia Kramar, Michael Loureiro, Justine Renard, Steven R Laviolette
Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28843863/administration-of-riluzole-to-the-basolateral-amygdala-facilitates-fear-extinction-in-rats
#8
Azusa Sugiyama, Misa Yamada, Akiyoshi Saitoh, Jun-Ichiro Oka, Mitsuhiko Yamada
A general understanding exists that inhibition of glutamatergic neurotransmission in the basolateral amygdala (BLA) impairs fear extinction in rodents. Surprisingly, we recently found that systemic administration of riluzole, which has been shown to inhibit the glutamatergic system, facilitates extinction learning in rats with a preconditioned contextual fear response. However, the mechanisms underlying this paradoxical effect of riluzole remain unclear. In this study, adult male Wistar rats were bilaterally cannulated in the BLA to examine the effects of intra-BLA administration of riluzole...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28842124/phencyclidine-induced-dysregulation-of-primary-cilia-in-the-rodent-brain
#9
Hiroki Shiwaku, Asami Umino, Masakazu Umino, Toru Nishikawa
Significant roles of the primary cilia in the central nervous system have been reported in neural generation and cognitive functions. However, little is known about the possible pathological changes in brain primary cilia in neuropsychiatric disorders. To obtain an insight into the relationship between cilial dysregulation and schizophrenia, we presently investigated the effects of psychotomimetics, phencyclidine, MK-801 (dizocilpine), and methamphetamine, on morphological and molecular indices in the rodent brain...
August 22, 2017: Brain Research
https://www.readbyqxmd.com/read/28840777/in-utero-exposure-to-alcohol-alters-reactivity-of-cerebral-arterioles
#10
Sergio G Cananzi, William G Mayhan
Our goal was to examine whether in utero exposure to alcohol impaired reactivity of cerebral arterioles during development. We fed Sprague-Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of pregnancy (21-23 days). Around 4-6 weeks after birth, we examined reactivity of cerebral arterioles to eNOS- (ADP) and nNOS-dependent (NMDA) agonists in the offspring. We found that in utero exposure to alcohol attenuated responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in rats exposed to alcohol in utero...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28838810/the-activation-of-nmda-receptors-alters-the-structural-dynamics-of-the-spines-of-hippocampal-interneurons
#11
Marta Pérez-Rando, Esther Castillo-Gómez, María Bellés, Héctor Carceller, Juan Nácher
N-Methyl-d-Aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play a key role in the structural plasticity of excitatory neurons, but to date little is known about their influence on the remodeling of interneurons. Among hippocampal interneurons, the somatostatin expressing cells in the CA1 stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change their density in response to different stimuli...
August 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28828606/glycine-transporters-and-its-coupling-with-nmda-receptors
#12
Francisco Zafra, Ignacio Ibáñez, David Bartolomé-Martín, Dolores Piniella, Marina Arribas-Blázquez, Cecilio Giménez
Glycine plays two roles in neurotransmission. In caudal areas like the spinal cord and the brainstem, it acts as an inhibitory neurotransmitter, but in all regions of the CNS, it also works as a co-agonist with L-glutamate at N-methyl-D-aspartate receptors (NMDARs). The glycine fluxes in the CNS are regulated by two specific transporters for glycine, GlyT1 and GlyT2, perhaps with the cooperation of diverse neutral amino acid transporters like Asc-1 or SNAT5/SN2. While GlyT2 and Asc-1 are neuronal proteins, GlyT1 and SNAT5 are mainly astrocytic, although neuronal forms of GlyT1 also exist...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28821660/contribution-of-astroglial-cx43-hemichannels-to-the-modulation-of-glutamatergic-currents-by-d-serine-in-the-mouse-prefrontal-cortex
#13
Claire Meunier, Nan Wang, Chenju Yi, Glenn Dallerac, Pascal Ezan, Annette Koulakoff, Luc Leybaert, Christian Giaume
Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine, a co-agonist of the NMDA receptor at the glycine-binding site, can be released by astrocytes in a calcium [Ca(2+)]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28807795/d-cycloserine-facilitates-extinction-learning-and-enhances-extinction-related-brain-activation
#14
Anne Klass, Benjamin Glaubitz, Martin Tegenthoff, Silke Lissek
Extinction learning is modulated by N-methyl d-aspartate receptors (NMDAR) particularly in prefrontal and hippocampal brain regions. The use of of NMDA agonists in exposure therapy of anxiety disorders has been investigated in various patient groups. Behavioral results showed beneficial effects of pre-learning administration of the partial NMDAR agonist d-Cycloserine (DCS) on therapy success. However, the impact of DCS upon non-fear-related contextual extinction, and associated recruitment of extinction-relevant brain regions is as yet unknown...
August 12, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28807674/phenylglycine-analogs-are-inhibitors-of-the-neutral-amino-acid-transporters-asct1-and-asct2-and-enhance-nmda-receptor-mediated-ltp-in-rat-visual-cortex-slices
#15
Alan C Foster, Natalie Rangel-Diaz, Ursula Staubli, Jia-Ying Yang, Mahmud Penjwini, Veena Viswanath, Yong-Xin Li
The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28803978/intraperitoneal-injection-of-d-serine-inhibits-high-fat-diet-intake-and-preference-in-male-mice
#16
Tsutomu Sasaki, Yasunobu Yasoshima, Sho Matsui, Hiromi Yokota-Hashimoto, Masaki Kobayashi, Tadahiro Kitamura
d-serine is a co-agonist of the N-methyl d-aspartate (NMDA) receptor, an important modulator of glutamatergic excitatory synaptic transmission. We previously reported that oral d-serine ingestion inhibited the intake of highly preferred food and promoted the intake of less preferred food in mice. Here, we analyzed the effects of intraperitoneal (IP) d-serine injections on feeding behavior in mice. We assessed the effects of d-serine during both the acquisition and maintenance of a preference for high-fat diets (HFDs)...
August 10, 2017: Appetite
https://www.readbyqxmd.com/read/28800869/the-role-of-ca3-gabab-receptors-on-anxiolytic-like-behaviors-and-avoidance-memory-deficit-induced-by-d-ap5-with-respect-to-ca-2-ions
#17
Shahram Zarrabian, Mohammad Nasehi, Maryam Farrahizadeh, Mohammad-Reza Zarrindast
Glutamatergic and GABAergic systems play key roles in the hippocampus and affect the pathogenesis of anxiety- and memory-related processes. Some investigations have assessed the role of balancing the function of these two systems in different areas of the central nervous system (CNS) as an approach to manage the related disorders. We investigated the anxiety and avoidance memory states using the test-retest protocol in the elevated plus maze to understand the role of GABAB receptors (GABABRs) in relation to the NMDA receptor blockade by D-AP5 (an NMDA receptor antagonist)...
October 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28795276/topiramate-via-nmda-ampa-kainate-gabaa-and-alpha2-receptors-and-by-modulation-of-creb-bdnf-and-akt-gsk3-signaling-pathway-exerts-neuroprotective-effects-against-methylphenidate-induced-neurotoxicity-in-rats
#18
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Tabassom Beiranvand, Shiva Mozaffari
Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist...
August 9, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28772090/nmda-receptors-in-the-dorsal-hippocampal-area-are-involved-in-tramadol-state-dependent-memory-of-passive-avoidance-learning-in-mice
#19
Majid Jafari-Sabet, Hamed Mofidi, Mohammad-Sadegh Attarian-Khosroshahi
The neurobiological mechanisms of tramadol abuse underlying the cognitive function are still imprecise. Considering these, the aim of the present study was to examine the possible effects of intra-CA1 injections of NMDA, an N-methyl-D-aspartate glutamate receptor (NMDAR) agonist and DL-AP5, a competitive NMDAR antagonist, on tramadol state-dependent memory. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training i.p. administration of an atypical MOR agonist, tramadol (2...
August 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28760974/structural-basis-of-subunit-selectivity-for-competitive-nmda-receptor-antagonists-with-preference-for-glun2a-over-glun2b-subunits
#20
Genevieve E Lind, Tung-Chung Mou, Lucia Tamborini, Martin G Pomper, Carlo De Micheli, Paola Conti, Andrea Pinto, Kasper B Hansen
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
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