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)

1. Monoamine neurotransmitters (epinephrine, norepinephrine, dopamine, serotonin and some of their metabolites (DOPEG, MHPG, DOPAC, 5-HIAA) were measured by HPLC in extracts from telencephalon (TEL) and diencephalon-midbrain (DM) before, during at the end of metamorphosis. 2. During metamorphosis MHPG increased and 5-HIAA decreased in TEL and DM while DOPEG decreased only in DM. 3. Monoamine levels were greater in the TEL and a larger increase in MHPG occurred there. 4. Captivity without metamorphosis also caused a significant depression of 5-HIAA in TEL and depression of DOPEG, MHPG and DOPAC in DM.
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PMID:Monoamines and their metabolites in the amphibian (Ambystoma tigrinum) brain: quantitative changes during metamorphosis and captivity. 135 51

Disturbed noradrenaline (NA) metabolism is thought to play a causal role in certain types of endogenic depression. This study was based on data from 88 patients with depression. The metabolism of NA was investigated by measuring urinary MHPG and plasma DOPEG concentrations and platelet nonoamine oxidase activity to determine if there were any differences in subgroups of depression defined by the DSM3. There was no difference in plasma DOPEG concentrations or of MAO activity in the different subgroups of depression, especially between episodes of major and non-major depression. On the other hand, depressed patients with an episode of major depression had significantly higher urinary MHPG concentrations than those with non-major depression.
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PMID:[Cerebral noradrenaline metabolism and classification of depression]. 356 12

We have analyzed the effects of agonists acting at different classes of metabotropic glutamate receptors (mGluRs) on paired pulse depression (PPD) at the medial perforant path/granule cell synapse. Drugs were bath applied and paired pulses delivered at 3-min intervals during control and during drug application. Both 1S,3R-1-aminocyclopentane- 1,3-dicarboxylic acid (1S,3R-ACPD, 100 microM), which acts at class I (mGluR1, 5) and class II (mGluR2, 3) mGluRs and L-2-amino-4-phosphobutyric acid (L-AP4, 100 microM) which is specific for class III (mGluR4, 6-8) mGluRs, strongly reduced PPD with an interstimulus interval (ISI) of 40 ms (P < 0.001). The class I specific agonists trans-azetidine-2,4,dicarboxylic acid (t-ADA, 100 microM) and 3,5,dihydroxyphenylglycine (DHPG, 100 microM) did not affect PPD. The relatively specific class II agonists S-3-carboxy-4-hydroxyphenylglycine (3C4HPG) and 2S,3S,4S-alpha- carboxycyclopropyl-glycine (L-CCG-I) did reduce PPD, but only at very high concentrations (500 and 40 microM respectively) with respect to their EC50 values. These results suggest that two types of mGluRs control PPD at this synapse--a class III mGluR and a class II-like mGluR, which may not correspond to one of the currently cloned receptors.
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PMID:Metabotropic glutamate receptor agonists reduce paired-pulse depression in the dentate gyrus of the rat in vitro. 750 Dec 46

It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose, on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.
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PMID:Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study. 892 74

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

The direct activation of metabotropic glutamate receptors (mGluRs) by 1S,3R-aminocyclopentane dicarboxylate (1S,3R-ACPD), has previously been shown to induce a relatively fast (maximum at 10 min) and slow (90 min) onset long-term potentiation (LTP) of synaptic transmission in the hippocampus. Here we report the first evidence for a relatively fast onset LTP of synaptic transmission in the immature male rat (50-100 g) dentate gyrus in vitro by application of the mGluR type I agonist, (S)-3,5-dihydroxyphenylglycine ((S)-DHPG; 20 microM). Bath application of (S)-DHPG caused a transient depression of the field excitatory postsynaptic potential (EPSP) slope, followed after washout by a relatively rapidly developing potentiation of synaptic transmission to a maximum increase at 12-15 min (161.1 +/- 11.4% compared to controls at 15 min; n = 8). This effect was not observed following perfusion with the enantiomer (R,S)-DHPG at the same dose. The (S)-DHPG potentiation occluded tetanically induced LTP and vice versa. The potentiation was antagonised by the non-specific mGluR antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine ((R,S)-MCPG) at high doses (500-1000 microM) but was unaffected in the presence of the N-methyl-D-aspartate (NMDA) receptor blocker, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 microM). Our results demonstrate a robust NMDA-independent LTP induced by (S)-DHPG that occludes tetanically induced LTP.
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PMID:Potentiation of synaptic transmission in the rat dentate gyrus in vitro by (S)-3,5-dihydroxyphenylglycine ((S)-DHPG). 922 94

The effects of glutamate metabotropic receptors (mGluRs) on excitatory transmission in the nucleus accumbens were investigated using electrophysiological techniques in rat nucleus accumbens slices. The broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentyl-1,3-dicarboxylate, the mGluR group 2 selective agonists (S)-4-carboxy-3-hydroxyphenylglycine, (1S,3S)-ACPD) and (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1), and the mGluR group 3 specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) all reversibly inhibited evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)-3,5-dihydroxyphenylglycine [(R,S)-DHPG] did not depress transmission. Dose-response curves showed that the rank order of agonist potencies was: L-CCG1 > L-AP4 > (1S,3S)-ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic mechanism, as they increased paired-pulse facilitation, decreased the frequency of miniature excitatory postsynaptic currents and had no effect on their amplitude. The mGluRs did not inhibit transmitter release by reducing voltage-dependent Ca2+ currents through N- or P-type Ca2+ channels, as inhibition persisted in the presence of omega-conotoxin-GVIA or omega-Aga-IVA. The depression induced by mGluRs was not affected by specific antagonists of dopamine D1, GABA-B or adenosine A1 receptors, indicating direct effects. Finally, (R,S)-DHPG specifically blocked the postsynaptic afterhyperpolarization current (I(AHP)). Our results represent the first direct demonstration of functional mGluRs in the nucleus accumbens of the rat.
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PMID:Metabotropic glutamate receptors in the rat nucleus accumbens. 924 Apr 9

Metabotropic glutamate receptors have been implicated in modulation of synaptic transmission in many different systems. This study reports the effects of selective activation of metabotropic glutamate receptors on synaptic transmission in intracellularly recorded locus coeruleus neurons in brain slice preparations. Perfusion of either L-2-amino-4-phosphonobutyric acid (L-AP4; 0.1-500 microM) or (+/-)-1-aminocyclopentane-trans-1,3,dicarboxylic acid (t-ACPD; 0.1-500 microM) caused a depression of excitatory postsynaptic potentials in a dose-dependent fashion to about 70% inhibition. Both agonists exerted their effects at relatively low concentrations with estimated EC50s of 2.6 microM and 11.5 microM for L-AP4 and t-ACPD, respectively. This inhibition was not observed with the potent group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 microM). Conversely, (R)-4-carboxy-3-hydroxyphenyl-glycine (4C-3H-PG), a group I antagonist/group II agonist, and 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a novel and specific group II agonist, also caused an inhibition of excitatory postsynaptic potentials. Both t-ACPD and L-AP4 produced an increase in paired-pulse facilitation, and failed to change the locus coeruleus response to focally applied glutamate, indicating a presynaptic locus of action. The L-AP4 inhibition was antagonized by (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4: group III antagonist) but not by (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG; mixed antagonist], suggesting that this agonist acts through a type 4 metabotropic glutamate receptor. Conversely, t-ACPD was antagonized by MCPG and by ethyl glutamate (group II antagonist), but not by aminoindan dicarboxylic acid (AIDA; group I antagonist) or MAP4, suggesting that this agonist acts on a type 2 or 3 metabotropic glutamate receptor. Taken together, these results suggest that two pharmacologically distinct presynaptic metabotropic glutamate receptors function in an additive fashion to inhibit excitatory synaptic transmission in locus coeruleus neurons. These receptors may be involved in a feedback mechanism and as such may function as autoreceptors for excitatory amino acids.
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PMID:Modulation of excitatory synaptic transmission in locus coeruleus by multiple presynaptic metabotropic glutamate receptors. 928 53

1. Glutamate (AMPA receptor-mediated) excitatory postsynaptic potentials (e.p.s.ps.), evoked by electrical stimulation rostral to the recording site, were examined by intracellular microelectrode recording from dopamine neurones in parasagittal slices of rat ventral midbrain. 2. The e.p.s.p. was depressed by the group III metabotropic glutamate (mGlu) receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4; 0.01-30 microM) by up to 60% with an EC50 of 0.82 microM. The depression induced by L-AP4 (3 microM) was reversed by the group III preferring mGlu receptor antagonist, alpha-methyl-4-phosphonophenylglycine (MPPG; 250 microM). 3. The group I and II mGlu agonist, 1S,3R-aminocyclopentanedicarboxylic acid (ACPD; 3-30 microM) also depressed the e.p.s.p. in a concentration-dependent manner. The effect of ACPD (10 microM) was reversed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 1 mM; 4 cells). This effect of ACPD was also partially antagonized (by 50.3+/-15.7%, 4 cells) by MPPG (250 microM). 4. The selective agonist at group I mGlu receptors, dihydroxyphenylglycine (DHPG; 100 microM), decreased e.p.s.p. amplitude by 27.1+/-8.2% (7 cells), as did the group II mGlu receptor-selective agonist (1S,1R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 microM) by 26.7+/-4.3% (5 cells). 5. DHPG (10-100 microM) caused a depolarization of the recorded cell, as did ACPD (3-30 microM), whereas no such postsynaptic effect of either L-AP4 or DCG-IV was observed. 6. These results provide evidence for the presence of presynaptic inhibitory metabotropic glutamate autoreceptors from the mGlu receptor groups II and III on descending glutamatergic inputs to midbrain dopamine neurones. Group I mGlu receptors mediate a postsynaptic depolarization, and can also depress glutamatergic transmission, but may not necessarily be localized presynaptically. These sites represent novel drug targets for treatment of schizophrenia and movement disorders of basal ganglia origin.
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PMID:Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro. 951 86

We have investigated the effect of a number of group I, II and III metabotropic glutamate (mGlu) receptor agonists and antagonists on paired pulse depression in the medial perforant path of the rat dentate gyrus in vitro. A triphasic pattern of a large depression at short intervals (10-50 ms), a reduction of this depression at intermediate intervals (50-200 ms) and again a large depression at late intervals (> 200 ms) was observed. The group I mGlu receptor agonist, (S)-3,5-dihydroxy phenylglycine ((S)-DHPG; 20 microM) had no significant effect on paired pulse depression at any interstimulus intervals. The mGlu receptor group II and III agonists, L-CCG-1 ((2S,3S,4S)-alpha-(carboxy-cyclopropyl)-glycine), DCG-IV ((2S,1'R,2'R,3'R)-2-2',3'-dicarboxy cyclopropylglycine), 1S,3R-ACPD (1S,3R-1-aminocyclopentate-1,3-dicarboxylic acid) and L-AP4 (L-2-amino-4-phosphono butyric acid) reduced paired pulse depression at interstimulus intervals of 200 ms or less. Application of the non specific mGlu receptor antagonist, MCPG (alpha-methyl carboxy-phenylglycine; 200 microM) completely inhibited the 1S,3R ACPD-induced reduction in paired pulse depression but was without effect on the L-AP4 response. The relatively specific group II antagonist MCCG ((2S,3S,4S)-2-methyl-2-carboxy cycloproprylglycine) at 200 microM and 500 microM, attenuated but did not completely inhibit the DCG-IV induced reduction of paired pulse depression. The putative group III pre-synaptic mGlu receptor antagonist alpha-methyl-L-AP4 and MSOP ((RS)-alpha-methylserine-O-phosphate) both at 200 microM inhibited the L-AP4-induced reduction in paired pulse depression at intermediate phase interstimulus intervals but not at early interstimulus intervals. These results specifically demonstrate the involvement of group III and III mGlu receptor ligands in the modulation of paired pulse depression in the medial perforant pathway.
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PMID:Group II and III metabotropic glutamate receptors modulate paired pulse depression in the rat dentate gyrus in vitro. 952 4


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