UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CA1 region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques. 2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 microM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential. 3. Ibotenate (25 microM) or L-glutamate (250 microM), in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 microM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 microM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current. 4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 microM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 microM). 5. The response to ionophoretic application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'. 6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult (greater than 80 days) slices. 7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP). 8. The results indicate that metabotropic glutamate receptor agonists suppress excitatory synaptic transmission in CA1 pyramidal cells by an action at a presynaptic site. This effect is developmentally regulated and is maximally expressed during the first postnatal month.
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PMID:Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus. 166 53

Activation of metabotropic glutamate receptors (mGluRs, QP or ACPD receptors) has recently been shown to cause depolarization, blockade of the slow after-hyperpolarization and depression of calcium currents in hippocampal pyramidal cells. Here, we report evidence for a new mGluR-mediated effect: slowing of the spike repolarization in CA1 cells in rat hippocampal slices. During blockade of the ionotropic glutamate receptors, the mGluR agonists trans-1-amino-cyclopentyl-1,3-dicarboxylate (t-ACPD), quisqualate or L-glutamate caused spike broadening. In contrast, the ionotropic receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) was ineffective. The spike broadening may act in concert with the other mGluR effects, e.g. by further increasing the influx of Ca2+ ions which, in turn, may contribute to synaptic modulation.
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PMID:Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons. 168 72

Long-term depression (LTD) in the intact cerebellum is a decrease in the efficacy of the parallel fiber-Purkinje neuron synapse induced by coactivation of climbing fiber and parallel fiber inputs. In cultured Purkinje neurons, a similar depression can be induced by iontophoretic glutamate pulses and Purkinje neuron depolarization. This form of LTD is expressed as a depression of alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA)-mediated current, and its induction is dependent on activation of metabotropic quisqualate receptors. The effect of inhibitors of protein kinase C (PKC) on LTD induction was studied. Inhibitors of PKC blocked LTD induction, while phorbol-12,13-diacetate (PDA), a PKC activator, mimicked LTD. These results suggest that PKC activation is necessary for the induction of cerebellar LTD.
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PMID:Participation of postsynaptic PKC in cerebellar long-term depression in culture. 172 Dec 43

A new non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist, GYKI 52466, was tested on L-glutamate (Glu)-, kainate (KAI)- and NMDA-induced responses in vivo, using both extracellular recording of antidromic field potentials and intracellular recording from rat abducens motoneurones. Intravenous (5-10 mg/kg) or iontophoretic applications of GYKI 52466 blocked the Glu-induced depression of antidromic field potentials only. Furthermore, intravenous application of ketamine blocked the NMDA-induced depression only. Iontophoretic application of GYKI 52466 reduced the Glu-induced neuronal depolarization but not those induced by NMDA and KAI. Our results show a selective blockade of Glu responses by GYKI 52466, probably by acting at the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subtype in rat abducens motoneurones.
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PMID:GYKI 52466 antagonizes glutamate responses but not NMDA and kainate responses in rat abducens motoneurones. 183 Mar 80

The acute effects of hypoxia and/or hypoglycaemia on DC potentials recorded from CA1 pyramidal neurones of the gerbil hippocampal slice maintained in vitro were investigated. Depolarizing potential changes were recorded when the slice was superfused with the excitatory amino acid agonists: NMDA (N-methyl-D-aspartic acid; 3-30 microM), AMPA ((RS)alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate; 1-30 microM), kainate (3-100 microM) and L-glutamate (1-10 mM). In response to a 20 min period of superfusion with an hypoxic artificial CSF solution at 30 degrees C, a transient depolarization occurred followed by a marked hyperpolarization. A further hyperpolarization occurred when superfusion of the slice with an oxygenated artificial CSF recommenced. Post-hypoxia, when the neurones had repolarized, the response to NMDA (10 microM) was less than the pre-hypoxic response. The extent of the depression of the NMDA response was found to depend on three variables: a) the duration of the period of hypoxia, b) the glucose concentration of the artificial CSF, and c) the temperature of the slice. As the duration of hypoxia was increased, the depression of the NMDA response was more marked. Reduction of the glucose concentration from 11 mM to 2 mM by partial substitution with sucrose (9 mM) made the tissues more sensitive to the effects of hypoxia, whereas reduction of the temperature from 30 degrees C to 20 degrees C made them less sensitive. The depression of the response to NMDA was observed over a range of concentrations of NMDA. The concentration response curve for AMPA was also flattened, however, the depolarizations in response to kainate or GABA were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hypoxia and hypoglycaemia on DC potentials recorded from the gerbil hippocampus in vitro. 209 Sep 52

The development of selective, systemically active alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists over the last 4 years has enabled the role of this excitatory amino acid receptor subtype to be scrutinised in the different models of ischaemia. The animal models of cerebral ischaemia can be subdivided into two major categories: focal ischaemia, in which the resulting infarct resembles the clinical condition of stroke; and models of severe forebrain ischaemia, in which there is delayed neuronal degeneration of hippocampal CA1 neurones. The neuropathology in the latter models resembles the clinical condition seen following a cardiac arrest, for example. It is well established that N-methyl-D-aspartate (NMDA) antagonists such as MK-801, 3-(2-carboxypiperazine-4-yl)-propenyl-1-phosphonate (CPPene), DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849), and N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine hydrochloride (CNS 1102) are neuroprotective in animal models of focal ischaemia. However, in models of severe forebrain ischaemia NMDA antagonists produced only partial protection. The discovery of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) as a systemically active AMPA receptor antagonist enabled the role of this receptor subtype in ischaemia to be investigated. NBQX was shown to be neuroprotective against delayed neuronal degeneration of hippocampal CA1 neurones in animal models of severe forebrain ischaemia. Recent studies have demonstrated that NBQX administration can be delayed by up to 12 h and amelioration of delayed neuronal degeneration of hippocampal CA1 neurones can still be seen. NBQX has also been shown to be neuroprotective in animal models of permanent and temporary middle cerebral artery occlusion. 1-(Aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a systemically active noncompetitive AMPA/kainate antagonist, was neuroprotective against focal ischaemia but was unable to attenuate hippocampal CA1 neuronal degeneration. Whilst the newer compounds such as (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl )-ethyl]-1,2,3,4,4a,5,6,7,8a-decahydroisoquinoline-3-carboxylic acid (LY 215490) and 6-(1-imidazolyl)-7-nitroquinoxaline-2,3(1H,4H)-dione (YM900) have been demonstrated to be neuroprotective in focal ischaemia models, there is still a lack of information with regard to their efficacy in models of severe forebrain ischaemia. It appears from initial studies that AMPA/kainate antagonists have a better behavioural profile than NMDA antagonists in terms of a lack of phychostimulant and phychotomimetic effects. However, these antagonists have their own problems in that they cause severe depression of glucose utilisation in the central nervous system at neuroprotective doses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists and their role in cerebral ischaemia. 752 37

1. The purpose of this study was to examine whether depolarizations evoked by excitatory amino acids can be recorded quantitatively, in vivo, with a microelectrode incorporated within a microdialysis probe. 2. Microdialysis probes incorporating a chlorided silver wire were implanted in the striatum of anaesthetized rats and perfused with artificial cerebrospinal fluid (ACSF). Increasing concentrations of excitatory amino acids were applied for 2 min via the microdialysis probe, and the extracellular direct current (d.c.) potential was recorded between the microdialysis electrode and a reference electrode placed under the scalp. 3. N-methyl-D-aspartate (NMDA, 25-500 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA, 5-1000 microM), kainate (5-500 microM), and glutamate (0.25-100 mM) evoked concentration-dependent depolarizations with maxima ranging from 7 to 10 mV, i.e. 3 to 10 times larger than those recorded from brain slices in vitro. Depolarizations evoked by glutamate receptor agonists applied by microdialysis shared several features with those recorded from brain slices. The most characteristic were: steep onset and recovery of NMDA and glutamate responses; marked post-depolarization hyperpolarization with NMDA; and very slow recovery after kainate application. At high concentrations (500 microM), NMDA occasionally initiated spreading depression. The relative potency of glutamate and NMDA was of the same order of magnitude to that obtained with the cortical wedge and hippocampal slices, glutamate being 100 to 400 times less potent than NMDA. 4. Two consecutive series of NMDA-stimuli within the same procedure evoked comparable depolarizations, indicating that reliable quantitative analysis of drug action can be performed, with each animal serving as its own control. This is relevant to the study of drugs acting on glutamate receptors especially antagonists. The remarkable inter-animal reproducibility is also a valuable feature.5. Pretreatment with dizocilpine maleate (MK-801, 2mgkg'1, i.p.) reduced by 65% the responses evoked by NMDA (500 fM). The non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX,100 1M) applied via the microdialysis probe reduced by around 78% the responses to AMPA and kainate (250 micro M). The fact that drugs, especially antagonists, can be administered either systemically, or directly through the dialysis probe to by-pass the blood-brain barrier or avoid peripheral effects, is especially relevant for neuropharmacological studies.6. Intracerebral microdialysis combined with in vivo recording of extracellular field potential is a novel and valuable method for the quantitative analysis of the action of drugs acting on glutamate receptors.This method should prove especially useful for comparing the sensitivity of specific brain structures to selective glutamate receptor agonists under normal conditions and when the neuronal micro environment is altered. It should also be useful for investigating the action of other depolarizing agents, such as veratridine, and their antagonists.
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PMID:Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo. 753 84

Expression of immediate early genes (IEGs) was examined following long-term desensitization of cerebellar Purkinje cells. This form of desensitization, which may underlie synaptic long-term depression (LTD), was evoked by co-administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and 8-bromo cGMP (8-Br-cGMP). Among the IEGS examined with in situ hybridization and immunohistochemistry, combined application of 8-Br-cGMP and AMPA synergistically enhanced the expression of c-Fos and Jun-B in Purkinje cells. This may suggest a role for active transcriptional complexes such as AP-1 (c-Fos/Jun-B), which could be formed following conjoint inputs to Purkinje cells and which may help to establish cerebellar long-term plasticity.
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PMID:The conjunctive stimuli that cause long-term desensitization also predominantly induce c-Fos and Jun-B in cerebellar Purkinje cells. 769 17

The ability of exogenous nitric oxide (NO) to modify synaptic transmission was investigated in area CA1 of the rat hippocampal slice. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (SNOG) depressed field excitatory postsynaptic potentials evoked by low frequency stimulation of the Schaffer collateral-commissural pathway. Upon washout of the NO donors, synaptic transmission rapidly returned to control levels. A similar reversible synaptic depression was produced by SNAP when tetanic stimulation (100 Hz; 1 s) was delivered in its presence. The effect of SNAP was not mimicked by its precursor or breakdown product and was blocked by haemoglobin, indicating that the effect involved NO. Roussin's black salt, a photolabile NO donor, also depressed transiently field excitatory postsynaptic potentials following photolysis. The depression was induced rapidly following a flash of UV light (20 s duration) focused onto the slice using a confocal microscope. The depressant effect of the NO donors on synaptic transmission was mimicked by zaprinast, a specific cGMP-phosphodiesterase inhibitor. Zaprinast depressed to a similar extent both the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptor-mediated components of excitatory postsynaptic currents without affecting passive membrane properties, indicating a presynaptic locus of action. SNAP, SNOG and zaprinast all elevated cGMP levels in rat hippocampal slices. Immunocytochemical staining revealed that the cGMP accumulation was mainly in a network of varicose fibres running throughout the CA1 region, consistent with a presynaptic site of action of NO. We conclude that NO, possibly through activation of guanylate cyclase, may be involved in transient presynaptic depression in the CA1 region of the hippocampus.
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PMID:The nitric oxide--cyclic GMP pathway and synaptic depression in rat hippocampal slices. 785 17

1. We have examined plasticity at glutamatergic synapses on neurons in slices of neostriatum, a forebrain area involved in movement and cognitive function. 2. High-frequency stimulation of afferent inputs to neostriatal neurons induced depression of glutamatergic synaptic transmission. Depression could be induced using either prolonged trains or short repetitive bursts of high-frequency stimulation. Depression developed within seconds after such stimulation. Responses recovered to baseline levels within 10 min in most slices but persisted for up to 60 min in others. 3. Postsynaptic passive electrical properties and the ability to elicit action potentials by postsynaptic depolarization were not altered during depression. 4. The magnitude and time course of depression was similar whether postsynaptic responses were mediated by alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or N-methyl-D-aspartate (NMDA) type glutamate receptors. Depression was not altered by antagonism of AMPA or NMDA receptors or potentiation of AMPA receptor function with aniracetam. 5. Depression was blocked by treatments that increase transmitter release including increased extracellular Ca2+, application of 4-aminopyridine, or application of phorbol ester. 6. Our findings indicate that glutamatergic synapses in neostriatum are capable of expressing a form of synaptic depression that may involve decreased glutamate release.
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PMID:Short- and long-term synaptic depression in rat neostriatum. 790 31

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