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

Intrathecal administration of glycine (strychnine) or GABA (bicuculline) but not opioid (naloxone), adrenergic (phentolamine) or serotonin (methysergide) receptor antagonists resulted in a dose-dependent organized agitation response to light tactile stimulation. This effect was maximally evoked by oscillating but not continuous stimulation applied to a dermatome corresponding to the levels of spinal cord acted upon by the intrathecal antagonist. Similar results were observed in chloralose-urethane anesthetized rats in which tactile stimulation evoked hypertensive responses following local tactile stimuli. The effects were only mildly depressed by even high doses of spinal morphine or DADL and not at all by ST-91 or baclofen. In contrast, intrathecal injections of glutamate receptor antagonists resulted in a dose-dependent depression of the strychnine evoked hyperesthesia with the ordering of activity being MK-801, AP-5, kynurenic acid, SKF10047 and ketamine. At doses below those which produced motor dysfunction, however, these agents had no effects on the hot-plate response latency. These data emphasize that low threshold afferent input is likely subject to an ongoing modulation, the loss of which results in a miscoding of the afferent stimulus yielding a pain relevant message. The lack of effect of agents having a powerful effect on somatic pain stimuli and the converse effects of glutamate receptor antagonists on the strychnine hyperesthesia at doses which do not affect the somatic pain response indicate discriminable processing systems, the characteristics of which resemble the clinical phenomenon observed in patients suffering from sensory dysesthesia following central and peripheral horn injury.
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PMID:Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. 254 67

The concentrations of 3 putative neurotransmitters (glutamate, aspartate and gamma-aminobutyrate), 4 related amino acids and 5 non-transmitter-related amino acids have been measured in neurosurgical samples (frontal cortex) from patients with intractable depression and controls. In addition, the glutamate receptor agonist 2-amino-4-sulpho-butanoic acid (homocysteic acid) has been identified in human brain and measured in these samples. There were no changes in the concentrations of amino acids in depressed patients compared to control with the exception of aspartic and homocysteic acids which were elevated in a sub-group of patients with depression compared to control. The Ca2+-dependent release (K+-stimulated) of putative neurotransmitters has been demonstrated for the first time from brain tissue of depressed patients. Glutamate release was unaltered from the control value. Aspartate values showed unexplained variability but it's release and that of gamma-aminobutyrate were elevated in some depressed subjects. These results do not support the hypothesis of reduced amino acid function in depressive illness.
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PMID:Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem. 257 Jun 24

Excitatory synaptic transmission, induced by electrical stimulation of optic nerve fibres on relay neurones, was recorded from in vitro preparations of the optic tectum of the frog. Bath-applied glutamate (the putative excitatory transmitter of the optic nerve) produced transient enhancement of tectal field potentials, followed by a depression, presumably caused by sustained neuronal depolarization. Pentobarbitone potently antagonized the depressant effect of glutamate, producing an approximate 50% reduction in the response of the tectum to glutamate at 25 microM. Midazolam also decreased the effect of glutamate with an IC50 value of 5 nM. Since, in the optic tectum of the frog, neither pentobarbitone nor midazolam enhance responses to bath-applied GABA, it is suggested that this area of the brain is a useful preparation in which to investigate the interaction of barbiturates and benzodiazepines with glutamate receptor mechanisms, without concurrent interactions with GABAergic processes.
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PMID:Antagonism of the actions of glutamate by pentobarbitone or midazolam in the frog optic tectum in vitro. 281 83

Phencyclidine (PCP) was tested on the metathoracic tibialis muscles of Locusta migratoria. In physiological solution, the peak amplitude of the excitatory postsynaptic currents (EPSCs) evoked by nerve stimulation was linearly related to membrane potential between -50 and -150 mV. The decay time constant of the EPSC (tau EPSC) was exponentially dependent on voltage and decreased with hyperpolarization. The membrane potential change required to produce an e-fold change in tau EPSC was 315 mV. PCP (5-40 microM) produced a concentration-dependent depression of both EPSC peak amplitude and tau EPSC. A slight nonlinearity in the current-voltage relationship could be discerned at high concentrations of PCP. The shortening of the decay time constant of EPSC (tau EPSC) occurred without significant change in the voltage sensitivity observed under control conditions. Under all experimental conditions, the decay of the EPSCs remained a single exponential of time. Fluctuation analysis indicated that 5 microM PCP shortens the lifetime of the glutamate-activated channels by 25.7 +/- 3%. PCP (10-80 microM) did not induced desensitization of the glutamate receptors. These results suggest that PCP interacts with the open conformation of ion channels activated by the glutamate receptor.
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PMID:Phencyclidine (PCP) blocks glutamate-activated postsynaptic currents. 286 72

We have investigated the effects of administration of exogenous glutamate receptor agonists on the amplitude of field excitatory post-synaptic potentials (fEPSPs) evoked in the CA1 region of the rat hippocampal slice by stimulation of the Schaffer collateral-commissural fibres. L-Glutamate applied by iontophoresis or by bath perfusion (50 microM for 5 min) evoked a slowly rising increase in the amplitude of the fESPS which persisted for over 90 min. L-Glutamate induced potentiation was blocked by either D(-)-2-amino-5-phosphonopentanoic acid (40 microM) or by (RS)-alpha-methyl-4-carboxyphenylglycine (500 microM). In slices in which synaptic long-term potentiation had been saturated, iontophoretically applied L-glutamate did not induce further potentiation, but reset the fEPSP amplitude back to control levels. Iontophoretic administration of N-methyl-D-aspartate (NMDA) evoked a transient potentiation which decayed back to control levels within 90 min whereas bath perfusion of NMDA (50 microM) evoked a persistent depression. Bath perfusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 50 microM) evoked no persistent effects. Bath administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 50 or 100 microM) caused a short term depression of the fEPSP and no significant persistent effects. Perfusion of 100 microM ACPD in medium containing 1 microM picrotoxin caused a much smaller short term depression of the fEPSP and this was followed by a gradually developing and persistent potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potentiation of synaptic transmission in the rat hippocampal slice by exogenous L-glutamate and selective L-glutamate receptor subtype agonists. 753 Aug 14

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

Hindlimb weight support and bipedal stepping occur after spinal cord transection in neonatal rats (birth to 12 days of age) while the same lesion in 15-day and older animals results in permanent loss of these responses. Some compensatory change in lumbar spinal circuitry must occur after spinal transection in young animals subserving these hindlimb behaviors. In contrast, animals just a few days older are incapable of such compensatory responses. We have examined the hypothesis that neural activity leads to the postnatal loss of plasticity in spinal circuitry. We find that antagonism of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor with MK-801 in young animals extends the sparing of hindlimb function after spinal transection to older animals. This effect is not due to a non-specific depression of all exciatory drive to motor neurons since Ia to motor neurons synaptic transmission through non-NMDA receptors is preserved during MK-801 treatment. Acute administration of MK-801 at the time of spinal transection or chronic administration of MK-801 after postnatal day 17 has no effect on recovery of hindlimb function after spinal transection. These results highlight the importance of NMDA receptor activation in spinal circuit maturation.
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PMID:NMDA antagonism during development extends sparing of hindlimb function to older spinally transected rats. 758 95

The effects of histamine on baseline synaptic transmission and long-term potentiation (LTP) were investigated in the CA1 region of rat hippocampal slices. Bath applied histamine reversibly and dose-dependently increased the amplitude of extracellularly recorded population spikes in the concentration range 0.1-100 microM by a maximum of 40%. At higher concentrations (10-100 microM) histamine also caused a small depression of field excitatory postsynaptic potentials (fEPSPs) of approx 10%. The effect of histamine on population spikes was found to be mediated through histamine H2 receptors. Histamine (10-100 microM) was found to produce a statistically significant LTP of fEPSPs when combined with a weak tetanus (0.25 sec, 50 Hz). Histamine H1 (mepyramine, 1 microM) and H2 (cimetidine, 50 microM) receptor antagonists did not block this enhanced potentiation. In addition, histamine (10-100 microM) enhanced the late portion of the response produced by pressure ejection of glutamate receptor agonist N-methyl-D-aspartate into the slice, as recorded extracellularly or intracellularly. This effect of histamine was only apparent when large NMDA responses were obtained, using a high pipette concentration of NMDA (1 mM). In the presence of histamine H1 and H2 antagonists, potassium channel blockers or blockade of inhibition, this enhancement could still be observed. We conclude that histamine facilitated the induction of LTP, most likely by acting directly at the NMDA receptor.
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PMID:Histaminergic modulation of synaptic plasticity in area CA1 of rat hippocampal slices. 761 44

Whole-cell voltage-clamp recordings were made in thin transverse slices from neurons of the dorsomedial subdivision of the nucleus of the tractus solitarius (NTS) of the rat. Cells were exposed to either the ionotropic glutamate receptor agonist (R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or the GABAA receptor agonist muscimol via pressure ejection directed at the cell soma. The metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 2-100 microM) reversibly depressed muscimol-evoked currents. Conversely, 1S,3R-ACPD reversibly potentiated AMPA-evoked currents. High-frequency stimulation of the tractus solitarius in the presence of 6,7-dinitroquinoxaline-2,3-dione and D-2-amino-5-phosphonopentanoic acid also produced a reversible depression of muscimol-evoked currents that was occluded in the presence of 100 microM 1S,3R-ACPD. 8-Br-cGMP or brain-derived natriuretic peptide mimicked the effects of 1S,3R-ACPD on AMPA and muscimol currents. However, agents that mimicked the actions of cAMP or diacylglycerol did not. These findings indicate that metabotropic glutamate receptors may mediate multiple components of excitatory transmission in the NTS including modulation of glutamate and GABA-activated ion channels.
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PMID:Activation of metabotropic glutamate receptors produces reciprocal regulation of ionotropic glutamate and GABA responses in the nucleus of the tractus solitarius of the rat. 768 73

In patch-clamped Purkinje cells (PCs), bath application of the ionotropic glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevents induction of long-term depression (LTD) of parallel fibre (PF)-mediated EPSPs by a pairing protocol between Ca2+ spike firing and PF stimulation whereas bath application of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate (mGLU) receptor antagonist, does not. On the other hand, LTD can be also induced by pairing direct depolarization of PCs with activation of mGLU receptors by 1S,3R-aminocyclopentyl-dicarboxylate (1S,3R-ACPD), even in the presence of CNQX. In this case, LTD induction is not consistently blocked by bath application of the nitric oxide synthase inhibitor, NG-methyl-L-arginine (L-NMMA), whereas it is strongly blocked when the protein kinase C inhibitor peptide 19-36 is dialysed into PCs. These results are at variance with LTD induced by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs which depends to the same extent on both cascades. Finally, thapsigargin, which depletes most intracellular Ca2+ pools, does not block induction of LTD by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs whereas it prevents the induction of LTD depending on strong mGLU receptor activation.
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PMID:Receptors and second messengers involved in long-term depression in rat cerebellar slices in vitro: a reappraisal. 771 36


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