Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat the effects of 25-100 microM of (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD), 1S,3R-ACPD and 1R,3S-ACPD, a metabotropic glutamate receptor (mGluR) agonist, on inward currents induced by glutamate (Glu), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate were studied under whole-cell voltage-clamp conditions. When the cells were clamped to -60 mV, the racemic mixture and both stereo isomers of trans-ACPD increase the responses elicited by Glu, AMPA, and NMDA, but little those of kainate. In addition, quisqualate (10-50 microM), in the presence of CNQX (5-20 microM) or NBQX (5 microM), potentiated NMDA-induced currents. The enhancing effect lasted 10-75 min, depending upon both dose and length of application. In a smaller proportion of dorsal horn neurons, the enhancing effect was preceded by a transient depression of the responses to Glu, AMPA, and NMDA. 2-Amino-3-phosphonopropionic acid (L-AP3), a putative antagonist of mGluR exerted little effect on responses to AMPA itself, but reduced or prevented the enhancing effect of 1S,3R-ACPD. It is concluded that activation of a metabotropic glutamate receptor by trans-ACPD, and its two enantiomers, may mediate the enhancement of AMPA and NMDA responses in acutely isolated rat spinal dorsal horn neurons. These results are consistent with the possibility that the activation of metabotropic glutamate receptor may contribute to the regulation of the strength of excitatory amino-mediated primary afferent neurotransmission, including nociception.
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PMID:Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid. 127 84

1. Intracellular recordings were made from pyramidal cells in area CA1 in mouse isolated hippocampal slices, after chronic ethanol treatment in vivo. 2. Fast i.p.s.ps were isolated by injection of the impaled neurones with QX314 (to block fast sodium currents and the slow i.p.s.p.) and stimulating the interneurones in the presence of the glutamatergic blockers, CNQX and APV. 3. The isolated fast-inhibitory postsynaptic potential (f.-i.p.s.p.) was measured at intervals during the 7 h withdrawal period. The reversal potential and sensitivity to bicuculline suggested that the isolated f.-i.p.s.p. was mediated by activation of the GABAA receptor-chloride ionophore complex. 4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of -50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ei.p.s.p., with no observed change in conductance, Gi.p.s.p. 5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings. 6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period. 7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of - 50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ejp.sp with no observed change in conductance, Gj ps p.5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings.6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period.7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.The increase in the f.-i.p.s.p. during the initial stages of the withdrawal might prevent the overt expression of epileptiform activity at this time.
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PMID:Changes in intrinsic inhibition in isolated hippocampal slices during ethanol withdrawal; lack of correlation with withdrawal hyperexcitability. 133 Jan 82

Spontaneous episodes of spreading depression (SD) were observed in the CA3 subfield of immature or young (2-30 days postnatally) hippocampal slices perfused with medium containing 4-aminopyridine (4-AP, 50 microM). SD appeared in 34% of the hippocampal slices examined and was more frequently observed in slices obtained from 11 to 20-day-old animals. SD studied with extracellular field potential recordings consisted of large amplitude (18.7 +/- 1.1 mV, mean +/- S.E.M.) negative DC shifts that lasted 30-250 s. Unlike the epileptiform activity that was concomitantly seen during 4-AP application, SD was blocked by the NMDA receptor antagonist 3-((RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 2-10 microM). In contrast, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 5 microM), a non-NMDA-type receptor antagonist, blocked the epileptiform activity but only increased the interval between SD episodes. These results demonstrate that immature hippocampal tissue is susceptible to SD episodes, when perfused with 4-AP-containing medium, and that the occurrence of these episodes presumably depends on the activation of the NMDA receptor. In addition these findings indicate that SD shows a sensitivity to excitatory amino acid receptor antagonists that differs from that of the epileptiform activity recorded simultaneously.
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PMID:CPP, an NMDA-receptor antagonist, blocks 4-aminopyridine-induced spreading depression episodes but not epileptiform activity in immature rat hippocampal slices. 134 14

1. The possibility of use-dependent, long-lasting modifications of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission was examined by intracellular recordings from granule cells of the hippocampal dentate gyrus in vitro. In the presence of the non-NMDA receptor antagonist 6-cyano-7-nitroquinaxaline-2,3-dione (CNQX, 10 microM) robust, long-term potentiation (LTP) of NMDA receptor-mediated synaptic potentials was induced by brief, high (50 Hz) and lower (10 Hz) frequency tetanic stimuli of glutamatergic afferents (60 +/- 6%, n = 8, P less than 0.001 and 43 +/- 12%, n = 3, P less than 0.05, respectively). 2. Hyperpolarization of granule cell membrane potential to -100 mV during 50-Hz tetanic stimuli reversibly blocked the induction of LTP (-6 +/- 2%, n = 6, P greater than 0.05) indicating that simultaneous activation of pre- and postsynaptic elements is a prerequisite for potentiation of NMDA receptor-mediated synaptic transmission. In contrast, hyperpolarization of the granule cell membrane potential to -100 mV during 10-Hz tetanic stimuli resulted in long-term depression (LTD) of NMDA receptor-mediated synaptic potentials (-34 +/- 8%, n = 8, P less than 0.01). 3. We also studied the role of [Ca2+]i in the induction of LTP and LTD of NMDA receptor-mediated synaptic responses. Before tetanization, [Ca2+]i was buffered by iontophoretic injections of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). BAPTA completely blocked the induction of LTP (3 +/- 5%, n = 13) and partially blocked LTD (-14.8 +/- 6%, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD. 135 Mar 6

GYKI 52466 is a specific antagonist of the neuronal excitation mediated by the non-NMDA type excitatory amino acid receptors, at several sites in the central nervous system. The experiments presented here show that the drug has a dose-dependent, slowly developing, long-lasting and reversible inhibitory action on the field potentials recorded from the CA1 region of the rat hippocampus, in vitro. Its action is similar to that of the well-known non-NMDA receptor blocker, CNQX. When the stimulus intensity-dependence of the population spikes was investigated, both drugs shifted the input-output curves in a parallel manner, while the maximum responses were only slightly depressed at the doses applied. With i.v. application, GYKI 52466 also inhibited the hippocampal field potentials recorded from the CA1 region of anesthetized rats dose-dependently. The inhibition was relatively weak compared to the effect found in earlier studies in the spinal cord, by the same doses. Four mg/kg i.v., a doses which is able to block spinal reflexes completely, caused an only about 20% depression of the recorded responses in the hippocampal CA1 area.
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PMID:Inhibition of hippocampal field potentials by GYKI 52466 in vitro and in vivo. 136 29

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

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.
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PMID:Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey. 168 74

1. High-threshold, slow inactivating inward Ca2+ currents were studied in CA1 pyramidal neurones from rat hippocampal slices using the single-electrode voltage clamp technique. 2. Kainate (50-400 nM) induced a dose-dependent depression of the amplitude of the slow Ca2+ current. At a dose of 200 nM the current amplitude was reduced from -0.63 +/- -0.06 to -0.32 +/- 0.06 nA. Such an effect of kainate was associated with the development of a small inward current (-0.11 +/- 0.03 nA). Kynurenic acid (1 mM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) fully prevented these actions of kainate. 3. The structurally related kainate analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 200 nM) depressed the slow Ca2+ current by 30 +/- 7%, an effect also blocked by CNQX. 4. In low-Na+ medium slow Ca2+ currents were followed by sustained inward tail currents. Kainate reduced both the steady-state Ca2+ current (from -0.98 +/- 0.14 to -0.63 +/- 0.15 nA) and the tail current (from -0.40 +/- 0.04 to -0.14 +/- 0.03 nA). 5. The inactivation process of the slow Ca2+ current was tested by a double-pulse protocol and was found to be enhanced by kainate. 6. Equimolar replacement of Ca2+ by Ba2+ produced larger inward currents followed by prolonged tails. Kainate reduced the Ba2+ steady-state current from -1.77 +/- 0.18 to -1.44 +/- 0.24 nA and the tail current from -0.47 +/- 0.15 to -0.17 +/- 0.05 nA. 7. In current clamp experiments Ca2+ action potentials were recorded from cells loaded with the Ca2+ chelator BAPTA. In these conditions kainate failed to reduce the Ca2+ action potential, while in the absence of BAPTA kainate shortened the Ca2+ action potentials by 30%. 8. It is suggested that low concentrations of kainate reduced the slow Ca2+ current by promoting its inactivation perhaps through a rise in free intracellular Ca2+.
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PMID:Depression of a sustained calcium current by kainate in rat hippocampal neurones in vitro. 177 Apr 44

Systemic administration of selective NMDA antagonists, such as CPP, APH, ketamine and MK-801, increased spontaneous gastric motility of the rat in a dose-dependent manner, and they prevented the NMDA-evoked depression of gastric motility. On the other hand, a broad spectrum excitatory amino acid antagonist, kynurenate, DNQX and CNQX decreased spontaneous gastric motility. Under the action of hexamethonium or chlorisondamine, CPP and MK-801 had little effect upon gastric motility. After the treatment with atropine, the motor responses to NMDA, CPP and MK-801 were hardly observed. Similar results were obtained after vagotomy.
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PMID:Selective N-methyl-D-aspartate (NMDA) antagonists increase gastric motility in the rat. 197 72

The effects of glycine on NMDA antagonism by a series of excitatory amino acid antagonists were tested in two functional in vitro models: NMDA induced [3H]GABA release from cultured mouse cortical neurons and NMDA evoked spreading depression in chick retina. In both models glycine reversed the NMDA antagonism by HA-966. Also NMDA block by kynurenic acid and by DNQX were partly reversed by glycine. However, CNQX, D-APV, ketamine and MK 801 showed the same NMDA antagonism in the absence and presence of glycine.
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PMID:Glycine reverses the effect of HA-966 on NMDA responses in cultured rat cortical neurons and in chick retina. 265 5


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