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)

We sought to determine whether metabotropic glutamate receptors contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in the nucleus of the solitary tract (NTS) in vivo. In alpha-chloralose-anesthetized rabbits, we determined the number of extracellular action potentials synaptically evoked by low (1 Hz)- or high-frequency vagal (3-20 Hz) or aortic depressor nerve (ADN) (6-80 Hz) stimulation and postsynaptically evoked by the ionotropic glutamate receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The metabotropic glutamate receptor agonist (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) attenuated NTS responses monosynaptically evoked by 1-Hz vagus stimulation by 34% (n = 25; P = 0.011), while augmenting AMPA-evoked responses by 64% (n = 17; P = 0.026). The metabotropic glutamate receptor antagonist alpha-methyl-4-phosphonophenylglycine (MPPG) did not affect NTS responses to low-frequency vagal stimulation (n = 11) or AMPA (n = 10) but augmented responses to high-frequency stimulation by 50% (n = 25; P = 0.0001). MPPG also augmented NTS responses to high-frequency ADN stimulation by 35% (n = 9; P = 0.048) but did not affect responses to low-frequency stimulation (n = 9) or AMPA (n = 7). The results suggest that metabotropic glutamate receptors, presumably at presynaptic sites, contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in NTS.
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PMID:Metabotropic glutamate receptors depress vagal and aortic baroreceptor signal transmission in the NTS. 981 76

Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-([[(1H-tetrazol-5-y l)methyl]oxy]methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3 -carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of approximately 0.60 microM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-D-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 microM ATPA (61 +/- 7% and 58 +/- 6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 microM) blocked the effects of 2 microM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 microM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82 +/- 10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus.
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PMID:The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus. 984 64

We examined actions of arginine vasopressin (AVP) and amastatin (an inhibitor of the aminopeptidase that cleaves AVP) on synaptic currents in slices of rat parabrachial nucleus using the nystatin-perforated patch recording technique. AVP reversibly decreased the amplitude of the evoked, glutamate-mediated, excitatory postsynaptic current (EPSC) with an increase in paired-pulse ratio. No apparent changes in postsynaptic membrane properties were revealed by ramp protocols, and the inward current induced by a brief application of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was unchanged after AVP. The reduction induced by 1 microM AVP could be blocked by a V(1) AVP receptor antagonist, [d(CH(2))(5)(1)-O-Me-Tyr(2)-Arg(8)]-vasopressin (Manning compound, 10 microM). Bath application of an aminopeptidase inhibitor, amastatin (10 microM), reduced the evoked EPSC, and AVP induced further synaptic depression in the presence of amastatin. Amastatin's effects also could be antagonized by the Manning compound. Corticotropin-releasing hormone slightly increased the EPSC at 1 microM, and coapplication with AVP attenuated the AVP response. Pretreatment of slices with 1 microg/ml cholera toxin or 0.5 microg/ml pertussis toxin for 20 h did not significantly affect AVP's synaptic action. The results suggest that AVP has suppressant effects on glutamatergic transmission by acting at V(1) AVP receptors, possibly through a presynaptic mechanism involving a pertussis-toxin- and cholera-toxin-resistant pathway.
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PMID:Vasopressin and amastatin induce V(1)-receptor-mediated suppression of excitatory transmission in the rat parabrachial nucleus. 1051 59

With increasing frequencies of autonomic afferent input to the nucleus tractus solitarii (NTS), postsynaptic responses are depressed. To test the hypothesis that a presynaptic mechanism contributes to this frequency-dependent depression, we used whole cell, voltage-clamp recordings in an NTS slice. First, we determined whether solitary tract stimulation (0.4-24 Hz) resulted in frequency-dependent depression of excitatory postsynaptic currents (EPSCs) in second-order neurons. Second, because decreases in presynaptic glutamate release result in a parallel depression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated components of EPSCs, we determined whether the magnitude, time course, and recovery from the depression were the same in both EPSC components. Third, to determine whether AMPA receptor desensitization contributed, we examined the depression during cyclothiazide. EPSCs decreased in a frequency-dependent manner by up to 76% in second- and 92% in higher-order neurons. AMPA and NMDA EPSC components were depressed with the same magnitude (by 83% and 83%) and time constant (113 and 103 ms). The time constant for the recovery was also not different (1.2 and 0.8 s). Cyclothiazide did not affect synaptic depression at >/=3 Hz. The data suggest that presynaptic mechanism(s) at the first NTS synapse mediate frequency-dependent synaptic depression.
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PMID:A presynaptic mechanism contributes to depression of autonomic signal transmission in NTS. 1051 69

We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CA1 region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu5 selective agonist 2-chloro-5-hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu1 and mGlu5 receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu1 selective antagonist (S)-2-methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu5 receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD.
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PMID:DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists. 1053 Aug 19

Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS.
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PMID:Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. 1077 32

In pentobarbitone-anaesthetized rats, the effects of two AMPA receptor antagonists, the competitive antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxaline (NBQX) and the non-competitive 2,3-benzodiazepine GYKI 53655, were compared on excitatory synaptic transmission of trigeminal origin in intracellularly-recorded abducens motoneurons. The effects of both antagonists were also investigated on the alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA)-, kainate-, and N-methyl-D-aspartate (NMDA)-induced depression of extracellular antidromic field potentials in the abducens motor nucleus. Microiontophoretic application (< or =100 nA) or intravenous injection of NBQX (< or =5 mg/kg) affected both AMPA- and kainate-induced depressions whereas GYKI 53655 (< or =100 nA; < or =4 mg/kg) blocked only the AMPA-induced depression. Neither NBQX or GYKI 53655 affected NMDA-induced depressions of antidromic field potentials. Using low intravenous (i.v.) doses of the antagonists NBQX or GYKI 53655 (2-2.5 mg/kg), a complete blockade of the composite disynaptic trigeminal excitatory post-synaptic potential (EPSP) was obtained without any changes in membrane potential, input resistance and antidromic action potentials in abducens motoneurons. GYKI 53655 was more potent at low i.v. doses (0.5-1.8 mg/kg) but NBQX had longer-lasting effects. The results show the existence of differences between the blocking action of NBQX and GYKI 53655 on AMPA-mediated receptor EPSP in abducens motoneurons.
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PMID:Blocking the trigeminal EPSP in rat abducens motoneurons in vivo with the AMPA antagonists NBQX and GYKI 53655. 1080 79

The effects of extracellular acidification on the synaptic function and neuronal excitability were investigated on the hippocampal CA1 neurons. A decrease of extracellular pH from 7.4 to 6.7 did not alter either the resting membrane potential or the neuronal membrane input resistance. Extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were significantly reduced by acidosis. Additionally, the amplitude of presynaptic fiber volley was also reduced. The sensitivity of postsynaptic neurons to N-methyl-D-aspartate, but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, was depressed by acidosis. Lowering of extracellular pH did not significantly affect the magnitude of paired-pulse facilitation (PPF) of synaptic transmission. Acidosis also reversibly limited the sustained repetitive firing (RF) of Na(+)-dependent action potentials elicited by injection of depolarizing current pulses into the pyramidal cells. The limitation of RF by extracellular acidification was accompanied by the reduction of the maximal rate of rise (;V(max)) of the action potentials and the amplitude of afterhyperpolarization. Neither the Na (+)/H (+) antiporter blocker 5-(N -ethyl -N -isopropyl)-amiloride nor the selective adenosine A (1) receptor antagonist 1,3-dipropyl -8-cyclopentylxanthine, however, affected the acidosis -induced synaptic depression. It was also found that acidosis did not affect either the induction r maintenance of long -term potentiation (LTP) at Schaffer collateral -CA 1 synapses. These results suggest that the extracellular acidosis -induced synaptic depression is likely to result from an inhibition of presynaptic Na (+) conductance, thereby decreasing the amplitude of action potentials in individual afferent fibers or the number of afferent fiber activation to stimuli and then indirectly affecting the signaling processes contributing to trigger neurotransmitter release.
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PMID:Influence of an extracellular acidosis on excitatory synaptic transmission and long-term potentiation in the CA1 region of rat hippocampal slices. 1105 10

How do drugs of abuse modify neural circuitry and thereby lead to addictive behaviour? As for many forms of experience-dependent plasticity, modifications in glutamatergic synaptic transmission have been suggested to be particularly important. Evidence of such changes in response to in vivo administration of drugs of abuse is lacking, however. Here we show that a single in vivo exposure to cocaine induces long-term potentiation of AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated currents at excitatory synapses onto dopamine cells in the ventral tegmental area. Potentiation is still observed 5 but not 10 days after cocaine exposure and is blocked when an NMDA (N-methyl-d-aspartate) receptor antagonist is administered with cocaine. Furthermore, long-term potentiation at these synapses is occluded and long-term depression is enhanced by in vivo cocaine exposure. These results show that a prominent form of synaptic plasticity can be elicited by a single in vivo exposure to cocaine and therefore may be involved in the early stages of the development of drug addiction.
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PMID:Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. 1138 72

The interactions between adenosine and NMDA receptors has been investigated using the paired-pulse paradigm in hippocampal slices. This technique allows the study of drug effects specifically at presynaptic terminals. The inhibitory effect of adenosine on population spikes, and the decrease of paired-pulse inhibition assessed using either population spikes or population excitatory postsynaptic potentials, were suppressed by performing the experiments in magnesium-free medium, or by superfusion of the slices with N-methyl-D-aspartate (NMDA) at a concentration (4 microM) which did not itself affect potential size. The suppressant effect of NMDA was prevented by 2-amino-5-phosphonopentanoic acid. All these interactions were still seen in the presence of bicuculline methobromide, 30 microM. Neither alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) nor kainate produced a suppression of adenosine responses. The presence of NMDA did not modify the effects of baclofen on population potentials or paired-pulse inhibition. Activating NMDA receptors by the induction of long-term potentiation or by superfusion with glycine also reduced significantly the effects of adenosine on population spikes and paired-pulse interactions. Increasing population potential size by a mechanism which did not involve the activation of NMDA receptors (increasing stimulus strength) did not change sensitivity to adenosine. When adenosine receptor-selective agonists were tested, it was found that NMDA did not modify the inhibitory effect of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine, but did enhance the excitatory effect of the adenosine A(2A) receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680). The combined response to NMDA and CGS21680 was prevented by the adenosine A(2A) receptor selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). It is concluded that NMDA receptor activation can suppress neuronal sensitivity to adenosine by acting at presynaptic sites, and that this interaction results from an increase in the excitatory action of adenosine A(2A) receptors, rather than a depression of A(1) receptor function.
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PMID:Suppression of presynaptic responses to adenosine by activation of NMDA receptors. 1155 59


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