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 rat cerebellar slices, 500 microM (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) reversibly inhibited both dendritic and somatic increases in FLUO-3 fluorescence intensity induced by bath applications of 50-100 microM (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD). No effect of MCPG was observed on dendritically recorded excitatory postsynaptic potentials evoked by synaptic activation of either parallel or climbing fibres. Long-term depression of parallel fibre-Purkinje cell transmission, induced either by conjunctive activation of parallel and climbing fibres or by pairing parallel fibre stimulation with intradendritic injections of 8-BrcGMP, was not only prevented in the presence of MCPG but a robust long-term potentiation of responses consistently occurred. These data show that metabotropic glutamate receptor activation is necessary for the induction of LTD.
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PMID:Induction of cerebellar long-term depression requires activation of glutamate metabotropic receptors. 806 Dec 95

The perforant path is the major excitatory cortical projection to the hippocampal dentate gyrus. Field potentials from the medial perforant path exhibit paired-pulse depression when evoked at interstimulus intervals of 40 to 800 msec. We found that an early component of paired-pulse depression recorded at interstimulus intervals of 40 to 100 msec from slices of rat hippocampus was reduced by L-2-amino-4-phosphonobutanoic acid (L-AP4) (20 microM) without a change in the size of the first field potential in the pair. Paired-pulse depression evoked at intervals of 200 to 800 msec was not reduced. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), DL-2-amino-3-phosphonopropionic acid and carbachol also reduced paired-pulse depression in a manner similar to L-AP4. Picrotoxin, phaclofen, theophylline or atropine did not reduce paired-pulse depression. Furthermore, paired-pulse depression (40-100 msec) does not appear to involve glutamate uptake or N-methyl-D-aspartate receptors as L-alpha-aminoadipate did not alter paired-pulse depression and neither trans-L-pyrrolidine-2,4-dicarboxylate and L-alpha-aminoadipate nor D-2-amino-5-phosphonopropionic acid blocked the effect of L-AP4 on paired-pulse depression. 4-Aminopyridine inhibits a potassium current that has a similar time course to the L-AP4-induced reduction of paired-pulse depression, however, paired-pulse depression was increased with exposure to 4-aminopyridine. These results indicate that the mechanism underlying paired-pulse depression consists of two components, the early component being reduced by L-AP4, 1S,3R-ACPD, DL-2-amino-3-phosphonopropionic acid and carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-2-amino-4-phosphonobutanoic acid and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid reduce paired-pulse depression recorded from medial perforant path in the dentate gyrus of rat hippocampal slices. 810 Dec 17

The effects of iontophoretically applied (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist of metabotropic glutamate receptors, were examined in rat cerebellar Purkinje cells in vivo. Multibarrel electrodes were used for extracellular recordings of spontaneous single unit discharges and iontophoretic ejection of 1S,3R-ACPD. The effect of 1S,3R-ACPD depended on both the strength and the duration of the iontophoretic current. Application of the agonist with ejection currents at or slightly above the response threshold for up to 60 s resulted in an increased rate of action potential firing. With larger ejection currents of the same duration the initial increase in activity was followed by a depression and eventually a cessation of activity. In the transition phase between low frequency firing and firing arrest, Purkinje cells generated almost exclusively complex spikes. When the drug application was continued for longer durations (1-10 min) the initial response was followed by a characteristic cyclic firing pattern. These cycles consisted of alternating phases of mainly simple spike activity, predominantly complex spike activity and silent intervals. At the end of drug applications using large ejection currents, a prolonged period (on average 66 s) with almost no spiking activity was observed. This period ended with an abrupt onset of simple spike firing. These findings point to an important function of cerebellar metabotropic glutamate receptors in the regulation of Purkinje cell activity.
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PMID:Multiphasic responses of cerebellar Purkinje cells to 1S,3R-ACPD: an in vivo study. 812 70

Perfusion of the 1S,3R isomer of trans-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 microM), or arachidonic acid (10 microM), for 5 min produced only depression of the field excitatory postsynaptic potential recorded in the CA1 region of rat hippocampal slices from which the CA3 region had been removed. However, perfusion of t-ACPD and arachidonic acid in combination induced a rapid potentiation of the response which in 4/6 slices was maintained for at least 90 min.
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PMID:Co-administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid and arachidonic acid potentiates synaptic transmission in rat hippocampal slices. 824 50

In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 microM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 microM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum.
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PMID:Heterogeneity of metabotropic glutamate receptors in the striatum: electrophysiological evidence. 827 36

1-Aminocyclopentane-trans-1S,3R-dicarboxylic acid (1S,3R-ACPD), a compound which selectively activates a metabotropic glutamate receptor (mGluR), suppresses hippocampal excitatory synaptic transmission. This depression is not antagonizable by L-2-amino-3-phosphonoproprionic acid (L-AP3), an agent which counteracts mGluR-induced phosphoinositide (PI) metabolism in several neuronal systems. Therefore, we believe that 1S,3R-ACPD activates a novel hippocampal mGluR subtype that is either insensitive to L-AP3 blockade and/or linked to an effector system that does not involve PI turnover.
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PMID:L-AP3 does not antagonize hippocampal synaptic depression induced by 1S,3R-ACPD. 838 41

1. The effect of the metabotropic glutamate receptor agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) on glutamatergic transmission at corticostriate synapses was examined using slices of neostriatum. Field potential recordings were performed in slices from adult animals, and the effects of t-ACPD on the synaptically driven population spike were examined. Tight-seal whole-cell recordings were made in slices from 2 to 4-wk-old rats, and effects of t-ACPD on the amplitude of excitatory postsynaptic potentials (EPSPs) and postsynaptic neuronal membrane properties were examined. In addition, the effects of putative metabotropic receptor agonists and antagonists and 4-aminopyridine were examined. The ability of these compounds to mimic t-ACPD or block its actions were determined. 2. Application of t-ACPD (5-100 microM) depressed the maximal amplitude of the synaptically driven population spike during field potential recording. This compound likewise depressed the amplitude of EPSPs observed with whole-cell recording. The 1S,3R isomer of t-ACPD was effective in depressing transmission, whereas the 1R,3S isomer was without effect at 50 microM. The cis isomer of ACPD (c-ACPD) also depressed transmission at concentrations from 25 to 100 microM. 3. Depression of population spike or EPSP amplitude by t-ACPD was not altered in the presence of the putative metabotropic receptor antagonist L-aminophosphonopropionic acid (AP3, 1 mM). In addition, the depressant action of t-ACPD on the population spike was not mimicked by aminophosphonobutyric acid, which has been shown to produce synaptic depression at other excitatory synapses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Properties of a presynaptic metabotropic glutamate receptor in rat neostriatal slices. 838 42

1. Neuropharmacological actions of a novel metabotropic glutamate receptor agonist, (2S,1'R,2'R,3'R)-2(2,3-dicarboxycyclopropyl)glycine (DCG-IV), were examined in the isolated spinal cord of the newborn rat, and compared with those of the established agonists of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD). 2. At concentrations higher than 10 microM, DCG-IV caused a depolarization which was completely blocked by selective N-methyl-D-aspartate (NMDA) antagonists. The depolarization was pharmacologically quite different from that caused by L-CCG-I and (1S,3R)-ACPD. 3. DCG-IV reduced the monosynaptic excitation of motoneurones rather than polysynaptic discharges in the nanomolar range without causing postsynaptic depolarization of motoneurones. DCG-IV was more effective than L-CCG-I, (1S,3R)-ACPD or L-2-amino-4-phosphonobutanoic acid (L-AP4) in reducing the monosynaptic excitation of motoneurones. 4. DCG-IV (30 nM-1 microM) did not depress the depolarization induced by known excitatory amino acids in the newborn rat motoneurones, but depressed the baseline fluctuation of the potential derived from ventral roots. Therefore, DCG-IV seems to reduce preferentially transmitter release from primary afferent nerve terminals. 5. Depression of monosynaptic excitation caused by DCG-IV was not affected by any known pharmacological agents, including 2-amino-3-phosphonopropanoic acid (AP3), diazepam, 2-hydroxysaclofen, picrotoxin and strychnine. 6. DCG-IV has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.
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PMID:A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord. 840 27

We have studied the effect of acute and chronic lithium treatment on the activity of striatal neurons recorded from corticostriatal slices. Under control conditions, tetanic stimulation of glutamatergic corticostriatal terminals caused long-term depression (LTD) of excitatory synaptic potentials. Acute lithium treatment did not affect the peak of the induction phase, but it reduced the following phases of LTD. LTD was completely blocked in slices obtained from rats chronically injected with LiCl. Lithium treatment failed to affect the intrinsic membrane properties of striatal neurons and the presynaptic inhibitory effects of carbachol and t-ACPD. We suggest that the lithium-induced blockade of LTD may contribute to the therapeutic action of lithium salts in mania and depression.
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PMID:Lithium treatment blocks long-term synaptic depression in the striatum. 849 46

We have investigated the role of metabotropic glutamate receptors (mGluR) in the induction of homosynaptic long-term depression (LTD) and depotentiation (DP) in the dentate gyrus of the adult rat. Perfusion of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) for a prolonged period (20 min) induced long-term depression (LTD) of field excitatory postsynaptic field potentials (epsps) from the baseline level and also depotentiation (DP) from the long-term potentiated level. Both the ACPD-and the low frequency stimulation (LFS)-induced LTD and DP were inhibited in the presence of the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), demonstrating the necessity for the activation of metabotropic glutamate receptors in the induction of LTD/DP. The LFS and ACPD-induced LTD were independent of the activation of N-methyl-D-aspartate (NMDA) receptors, as they were not blocked by the NMDA receptor antagonist D-2-amino-5-phophonopentanoate (AP5).
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PMID:Metabotropic glutamate receptor-induced homosynaptic long-term depression and depotentiation in the dentate gyrus of the rat hippocampus in vitro. 853 79


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