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)

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

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

1. The depression of synaptic transmission by the specific metabotropic glutamate receptor (mGlu) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) was investigated in area CA1 of the hippocampus of 4-10 week old rats, by use of grease-gap and intracellular recording techniques. 2. In the presence of 1 mM Mg2+, (1S,3R)-ACPD was a weak synaptic depressant. In contrast, in the absence of added Mg2+, (1S,3R)-ACPD was much more effective in depressing both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of synaptic transmission. At 100 microM, (1S,3R)-ACPD depressed the slope of the field excitatory postsynaptic potential (e.p.s.p.) by 96 +/- 1% (mean +/- s.e.mean; n = 7) compared with 23 +/- 4% in 1 mM Mg(2+)-containing medium (n = 17). 3. The depressant action of 100 microM (1S,3R)-ACPD in Mg(2+)-free medium was reduced from 96 +/- 1 to 46 +/- 6% (n = 7) by the specific NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 100 microM). 4. Blocking both components of GABA receptor-mediated synaptic transmission with picrotoxin (50 microM) and CGP 55845A (1 microM) in the presence of 1 mM Mg2+ also enhanced the depressant action of (1S,3R)-ACPD (100 microM) from 29 +/- 5 to 67 +/- 6% (n = 6). 5. The actions of (1S,3R)-ACPD, recorded in Mg(2+)-free medium, were antagonized by the mGlu antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). Thus, depressions induced by 30 microM (1S,3R)-ACPD were reversed from 48 +/- 4 to 8 +/- 6% (n = 4) by 1 mM (+)-MCPG. 6. In Mg(2+)-free medium, a group I mGlu agonist, (RS)-3, 5-dihydroxyphenylglycine (DHPG; 100 microM) depressed synaptic responses by 74 +/- 2% (n = 18). In contrast, neither the group II agonists ((2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine; L-CCG-1; 10 microM; n = 4) and ((2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine; DCG-IV; 100 nM; n = 3) nor the group III agonist ((S)-2-amino-4-phosphonobutanoic acid; L-AP4; 10 microM; n = 4) had any effect. 7. The depolarizing action of (1S,3R)-ACPD, recorded intracellularly, was similar in the presence and absence of Mg(2+)-AP5 did not affect the (1S,3R)-ACPD-induced depolarization in Mg(2+)-free medium. Thus, 50 microM (1S,3R)-ACPD induced depolarizations of 9 +/- 3 mV (n = 5), 10 +/- 2 mV (n = 4) and 8 +/- 2 mV (n = 5) in the three respective conditions. 8. On resetting the membrane potential in the presence of 50 microM (1S,3R)-ACPD to its initial level, the e.p.s.p. amplitude was enhanced by 8 +/- 3% in 1 mM Mg2+ (n = 5) compared with a depression of 37 +/- 11% in the absence of Mg2+ (n = 4). Addition of AP5 prevented the (1S,3R)-ACPD-induced depression of the e.p.s.p. (depression of 4 +/- 5% (n = 5)). 9. It is concluded that activation by group 1 mGlu agonists results in a depression of excitatory synaptic transmission in an NMDA receptor-dependent manner.
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PMID:NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus. 893 29

1. Neuropharmacological actions of all the possible stereoisomers of 3',3'-difluoro-2-(carboxycyclopropyl)glycine (3',3'-difluoro-CCG) were compared with those of the corresponding 2-(carboxycyclopropyl)glycine (CCG) isomers in the isolated spinal cord of newborn rats. (2S,1'S,2'S)- and (2S,1'R,2'S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F2CCG-I and L-F2CCG-IV) were the most potent in causing depolarization, their threshold concentrations being approximately 1 microM. 2. The depolarization evoked by L-F2CCG-I (30 microM) was depressed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM (n=4)) to 17+/-3% of the control: this depolarizing action was not decreased by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM), and only slightly decreased by high concentrations of D-2-amino-5-phosphonopentanoic acid (D-AP5, 100 microM), suggesting that L-F2CCG-I activates mainly metabotropic glutamate receptors. 3. L-F2CCG-I preferentially depressed the monosynaptic component of the spinal reflex approximately 3 times more effectively than (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I). The depressant action of L-F2CCG-I (0.2 microM-0.7 microM) on monosynaptic excitation was antagonized by (2S,1'S,2'S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG, 0.3 mM-1 mM) and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 0.3 mM). 4. DL-alpha-aminopimelate (10 and 100 microM) selectively potentiated the depression of monosynaptic excitation caused by L-CCG-I (0.2 microM) and L-F2CCG-I (0.1 microM). The actions of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (50 nM-0.2 microM), L-2-amino-4-phosphonobutanoic acid (L-AP4) (0.3-1 microM), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) (1-7 microM) and baclofen (0.1-0.7 microM) were unaffected by DL-alpha-aminopimelate. The threshold concentration for the potentiating actions of DL-alpha-aminopimelate was 3 microM. 5. The depolarization induced by quisqualate (3 microM, 10 s application) was increased to 115+/-2% and 137+/-5% of the control values during combined application of quisqualate with either 30 microM or 100 microM DL-alpha-aminopimelate, respectively. 6. Following the application and subsequent washout of L-F2CCG-I, DL-alpha-aminopimelate (3-100 microM) decreased the amplitude of the monosynaptic component of spinal reflexes in a concentration-dependent manner, indicating a 'priming' effect of L-F2CCG-I.
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PMID:Potentiation by DL-alpha-aminopimelate of the inhibitory action of a novel mGluR agonist (L-F2CCG-I) on monosynaptic excitation in the rat spinal cord. 951 98

Hippocampal long-term depression (LTD) involves a long-lasting decrease in synaptic transmission which is induced by low-frequency stimulation (LFS). Evidence exists that variability in the responsiveness of rat strains to LFS occurs. Thus, Wistar rats readily express LTD in vivo, whereas Hooded Lister rats demonstrate at best short-term depression (STD) in response to LFS. Group III metabotropic glutamate receptor (mGluR)-involvement in the induction of LTD in freely moving rats has not yet been investigated. This study therefore examined the effect of group III mGluR activation and inhibition on LTD expression, and evaluated these effects in Wistar and Hooded Lister rats. Animals were chronically implanted with recording and bipolar stimulating electrodes in the CA1 region, and an injection cannula in the lateral cerebral ventricle. LFS (1 Hz, 900 pulses) induced LTD in Wistar, and STD in Hooded Lister rats. Agonist priming with L-2-amino-4-phosphonobutanoic acid (AP4, 400 nmol/5 microl) facilitated LTD expression in Hooded Lister but not Wistar rats. The antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine inhibited the facilitatory effects of AP4 in Hooded Lister- and impaired LTD expression in Wistar rats. These data imply a role for group III mGluRs in hippocampal LTD in vivo, and suggest that differences in this mGluR system may account, in part, for strain-dependent variations in LTD expression.
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PMID:Group III metabotropic glutamate receptors modulate long-term depression in the hippocampal CA1 region of two rat strains in vivo. 1096 39

1. The group II metabotropic glutamate (mGlu) receptor antagonist (2S,1'S,2'S)-2-(2-carboxycyclopropyl)-2-(9H-xanthen-9-yl)glycine (LY341495) also has activity at group I and III mGlu receptors at higher concentrations and can be used to discriminate between mGlu receptor subtypes. We report the antagonist action of LY341495 on glutamate receptors expressed in the neonatal rat spinal cord preparation and the use of this antagonist to investigate the group III mGlu receptor subtypes responsible for mediating the depression of synaptic transmission in the spinal cord mediated by the group III mGlu receptor agonists (S)-2-amino-4-phosphonobutanoic acid ((S)-AP4) and (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-I). 2. LY341495 antagonised mGlu receptor agonist-induced responses in the spinal cord with a rank order of potency of group II > group III > group I, which is the same as that observed in human cloned mGlu receptor cell lines. Antagonism of group II and III mGlu receptor-mediated effects were time dependent when low-nanomolar concentrations of LY341495 were used. Although the rank order of potency of LY341495 was the same on native rat and cloned human mGlu receptors, there was a compression in the selectivity between group II and III mGlu receptors, expressed in the spinal cord. 3. In agreement with a previous study on cloned ionotropic glutamate receptors 100 microM LY341495 had little or no effect on N-methyl-D-aspartate, (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid or kainate receptor-mediated responses on motoneurones. 4. LY341495 exhibited low-nanomolar potency antagonist activity against (S)-AP4 and ACPT-I suggesting that these agonists are activating predominantly mGlu8 and that mGlu4 receptors do not play a role in modulating synaptic transmission in the pathways stimulated in the experiments described here.
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PMID:Actions of LY341495 on metabotropic glutamate receptor-mediated responses in the neonatal rat spinal cord. 1274 33

We investigated whether group III metabotropic glutamate (mGlu) receptors are critically involved in the expression of long-term potentiation (LTP), depotentiation, or long-term depression (LTD) in the dentate gyrus of freely moving rats. Male Wistar rats (7 8 weeks) underwent implantation of stimulating and recording electrodes in the medial perforant path and dentate gyrus granule cell layer, respectively. A cannula was permanently implanted into the ipsilateral cerebral ventricle to enable drug administration. Intracerebral injection of the group III mGlu receptor agonist, L(+)-2-amino-4-phosphonobutanoic acid (AP4), significantly inhibited LTP at a concentration which unaffects basal synaptic transmission. Depotentiation. short-term depression (STD) and LTDwere unaffected by the agonist. The antagonist. (R.S)-r-cyclopropyl-4-phosphonophenylglycine (CPPG), inhibited agonist effects. but had no independent effects on basal synaptic transmission. CPPG did not affect the profile of LTP, depotentiation or STD elicited by low frequency stimulation (LFS) at 0.5 or 3 Hz. but significantly impaired LTD expression (at I Hz) and STD elicited at 5 Hz. These findings suggest that activation of group III mGlu receptors is critically required for LTD. but not LTP or depotentiation in the dentate gyrus and provide evidence for the involvement of separate mechanisms underlying LTD and depotentiation.
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PMID:Role of the group III metabotropic glutamate receptor in LTP, depotentiation and LTD in dentate gyrus of freely moving rats. 1508 77

In vivo, activation of group III metabotropic glutamate (mGlu) receptors leads to a reduction of basal synaptic transmission in the hippocampus, and depending on the experimental conditions in vitro, leads to neuroprotection or neurotoxicity. Here, the cellular response to cerebral application of L(+)-2-amino-4-phosphonobutanoic acid (AP4) was investigated in the CA1 region and dentate gyrus of freely moving rats. Drugs were applied via the lateral ventricle, and electrophysiological measurements were obtained via chronically implanted electrodes. AP4 produced a slowly developing depression of evoked responses in both hippocampal regions which lasted for over 4 h. Effects could be reversed by application of high frequency tetanus. Histological evaluation, 4 h or 7 d, following a single, acute AP4 injection into the lateral cerebral ventricle showed that AP4-mediated synaptic depression either amplified (CA1) or attenuated (dentate gyrus) excitotoxic neuronal death, strongly depending on the sub-region investigated. Effects were long-lasting, being still evident 7 days after AP4 application. In both hippocampal areas, the effects obtained were subtle, however, with the CA1 region being more potently affected. Interestingly, effects in the dentate gyrus comprised a slight enhancement of live cell number coupled with deterioration in cell area, suggesting that cell proliferation triggered by group III mGlu receptor activation may have masked neurotoxic effects mediated by activation of this receptor. These results show that although AP4 induces a slow-onset synaptic depression in both sub-regions, cell viability is differentially influenced by activation of group III mGlu receptors in the CA1 region and dentate gyrus.
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PMID:Group III metabotropic glutamate receptor-mediated, chemically induced long-term depression differentially affects cell viability in the hippocampus. 1654 66

The metabotropic glutamate receptor 7a (mGluR7a), a heptahelical Galphai/o-coupled protein, has been shown to be important for presynaptic feedback inhibition at central synapses and certain forms of long term potentiation and long term depression. The intracellular C terminus of mGluR7a interacts with calmodulin in a Ca2+-dependent manner, and calmodulin antagonists have been found to abolish presynaptic inhibition of glutamate release in neurons and mGluR7a-induced activation of G-protein-activated inwardly rectifying K+ channel (GIRK) channels in HEK293 cells. Here, we characterized the Ca2+ dependence of mGluR7a signaling in Xenopus oocytes by using channelrhodopsin-2 (ChR2), a Ca2+-permeable, light-activated ion channel for triggering Ca2+ influx, and a GIRK3.1/3.2 concatemer to monitor mGluR7a responses. Application of the agonist (S)-2-amino-4-phosphonobutanoic acid (l-AP4) (1-100 microm) caused a dose-dependent inward current in high K+ solutions due to activation of GIRK channels by G-protein betagamma subunits released from mGluR7a. Elevation of intracellular free Ca2+ by light stimulation of ChR2 markedly increased the amplitude of L-AP4 responses, and this effect was attenuated by the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). l-AP4 responses were potentiated by submembranous [Ca2+] levels within physiological ranges and with a threshold close to resting [Ca2+]i values, as determined by recording the endogenous Xenopus Ca2+-activated chloride conductance. Together, these results show that L-AP4-dependent mGluR7a signaling is potentiated by physiological levels of [Ca2+]i, consistent with a model in which presynaptic mGluR7a acts as a coincidence detector of Ca2+ influx and glutamate release.
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PMID:Increases in intracellular calcium triggered by channelrhodopsin-2 potentiate the response of metabotropic glutamate receptor mGluR7. 1859 84