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 a double blind placebo-controlled investigation it was shown that transcranial electric treatment (TET), comprising the combination of a constant current with a pulse current of square impulses of 70-80 Hz is an effective method to correct affective disturbances (anxiety, depression) in alcoholic patients. The medical effects of TET are accompanied by changes in the metabolism of GABA and monoamines, but not of beta-endorphin, and also by a decrease in the latency of alpha-rhythm appearance after closing of the eyes.
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PMID:The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients. 202 55

The acute effects of hypoxia and/or hypoglycaemia on DC potentials recorded from CA1 pyramidal neurones of the gerbil hippocampal slice maintained in vitro were investigated. Depolarizing potential changes were recorded when the slice was superfused with the excitatory amino acid agonists: NMDA (N-methyl-D-aspartic acid; 3-30 microM), AMPA ((RS)alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate; 1-30 microM), kainate (3-100 microM) and L-glutamate (1-10 mM). In response to a 20 min period of superfusion with an hypoxic artificial CSF solution at 30 degrees C, a transient depolarization occurred followed by a marked hyperpolarization. A further hyperpolarization occurred when superfusion of the slice with an oxygenated artificial CSF recommenced. Post-hypoxia, when the neurones had repolarized, the response to NMDA (10 microM) was less than the pre-hypoxic response. The extent of the depression of the NMDA response was found to depend on three variables: a) the duration of the period of hypoxia, b) the glucose concentration of the artificial CSF, and c) the temperature of the slice. As the duration of hypoxia was increased, the depression of the NMDA response was more marked. Reduction of the glucose concentration from 11 mM to 2 mM by partial substitution with sucrose (9 mM) made the tissues more sensitive to the effects of hypoxia, whereas reduction of the temperature from 30 degrees C to 20 degrees C made them less sensitive. The depression of the response to NMDA was observed over a range of concentrations of NMDA. The concentration response curve for AMPA was also flattened, however, the depolarizations in response to kainate or GABA were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hypoxia and hypoglycaemia on DC potentials recorded from the gerbil hippocampus in vitro. 209 Sep 52

The present study investigates the effects of GABAA- and GABAB-receptor agonists and antagonists on gastric secretion after their i.c.v. administration to conscious pylorus-ligated rats and anaesthetized stomach lumen-perfused rats. Muscimol was without effect in pylorus-ligated rats, whereas baclofen produced a significant decrease in acid secretion, which was fully prevented by phaclofen. Under these conditions, a significant decrease in acid secretion was also obtained with bicuculline. In stomach lumen-perfused rats, muscimol caused a marked, dose-dependent increase in acid secretion, which was antagonized by bicuculline. Under the same conditions, baclofen induced a moderate, but significant, bicuculline-sensitive increase in acid secretion. Overall, our results suggest the presence of two central GABA pathways which mediate opposite effects: (a) a bicuculline-sensitive GABAA-receptor, the stimulation of which increases acid secretion under pharmacological depression of central vagal tone (anaesthetized rats); (b) a phaclofen-sensitive GABAB-receptor, the activation of which decreases vagally stimulated acid secretion (pylorus-ligated rats).
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PMID:Central GABAA excitatory and GABAB inhibitory receptors regulate gastric acid secretion in rats. 215 8

Behavioral and electrophysiological evidence implicating the GABA-benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy was obtained using an improved rat model of hepatic encephalopathy caused by thioacetamide-induced fulminant hepatic failure. After the administration of thioacetamide together with supportive therapy, acute hepatocellular failure developed in rats as a result of massive hepatocellular necrosis without evidence of renal failure or hypoglycemia. The evolution of hepatic encephalopathy in this model was sufficiently slow to readily permit the staging of the syndrome. Prominent features of the encephalopathy include a marked reduction in open field activity and an abnormal visual evoked response. Both the deficits in spontaneous motor function and visual evoked response abnormalities of rats in stages III to IV hepatic encephalopathy were significantly improved after the administration of the benzodiazepine receptor ligands flumazenil or Ro 15-4513. Doses of flumazenil or Ro 15-4513 that produced these effects in rats with hepatic encephalopathy had no detectable action on either the behavior or the visual evoked responses of normal rats. The ability of benzodiazepine receptor ligands to ameliorate both the behavioral depression and the visual evoked response abnormalities associated with hepatic encephalopathy in the thioacetamide-induced rat model suggest an involvement of the GABA/benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy. In addition, the similarity of these observations to those in rabbits with hepatic encephalopathy caused by galactosamine-induced fulminant hepatic failure is compatible with the hypothesis that the mechanisms of hepatic encephalopathy in these two distinct models share a common final pathway, the allosteric enhancement of GABAergic tone through the benzodiazepine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor ligands. 215 65

1. Intracellular recordings were made from antidromically identified motoneurones in transverse spinal cord slices from neonatal (12-16 day) rats. 2. Superfusion of (+/-)-baclofen (0.5-50 microM) reduced the excitatory postsynaptic potentials (e.p.s.ps) and inhibitory postsynaptic potentials (i.p.s.ps) evoked by dorsal root or dorsal root entry zone stimulation in a concentration-dependent manner; the calculated EC50 was 2.4 microM. Baclofen in comparable concentrations also reversibly eliminated spontaneously occurring e.p.s.ps and i.p.s.ps. 3. (-)-Baclofen was more effective as compared to baclofen in reducing the synaptic responses, whereas (+)-baclofen at concentrations as high as 50 microM was ineffective. 4. Baclofen (less than 5 microM) attenuated the synaptic responses without causing a significant change of passive membrane properties and depolarizations induced by exogenously applied glutamate. In addition to synaptic depression, baclofen (greater than 5 microM) caused a hyperpolarization associated with decreased membrane resistance in some of the motoneurones; the glutamate responses were also attenuated. 5. Baclofen reversibly depressed the spike after-hyperpolarization of the motoneurones. 6. GABA (1-10 mM) depressed synaptic transmission and depolarized or hyperpolarized motoneurones. While potentiated by the uptake inhibitor nipecotic acid, the synaptic depressant effect of GABA was not antagonized by bicuculline. 7. The synaptic depressant effect of baclofen was neither blocked by GABAA antagonists bicuculline and picrotoxin (10-50 microM) nor by the GABAB antagonist phaclofen (0.1-1 mM). 8. It is suggested that baclofen depresses excitatory and inhibitory transmission in rat motoneurones by primarily a presynaptic mechanism in reducing the liberation of chemical transmitters from nerve endings via a phaclofen-insensitive GABAB receptor.
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PMID:Phaclofen-insensitive presynaptic inhibitory action of (+/-)-baclofen in neonatal rat motoneurones in vitro. 215 78

During the past decade a new approach to pathogenetic studies of hepatic encephalopathy has been undertaken to identify the neurochemical alterations which characterize the syndrome. Using animal models of hepatic encephalopathy electrophysiological, behavioral, pharmacological and biochemical evidence were provided of an increased functional activity of the GABA-A receptors, including the Benzodiazepine site. These demonstrations seem to explain the increased sensitivity of patients with acute or chronic liver disease to sedative administration. The described increased tone of the GABAergic receptor complex seems to play a key role in the generalized depression of the central nervous system which characterizes hepatic encephalopathy, but other factors seem to contribute to the neuronal derangement present in this syndrome leading to an imbalance between inhibitory and excitatory receptor systems in the brain. Based on these findings a new symptomatic treatment with anti-benzodiazepine compounds which seem temporarily to counteract the symptoms of hepatic encephalopathy, was introduced.
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PMID:Supersensitivity of GABA-A receptors in hepatic encephalopathy. 215 20

Recent advances in the psychopharmacology of GABA synapses are reviewed. The usefulness of GABA mimetics in tardive dyskinesia and epilepsy has been confirmed, as has a dysfunction of GABA synapses in the etiopathology of these conditions. The antidepressant profile of GABA agonists in animal models for depression has been extended. The role of GABA receptors in the mechanism of action of antidepressants has been further delineated, with a parallelism occurring between the behavioral and biochemical response to antidepressant drug treatment in different animal models of depression.
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PMID:The psychopharmacology of GABA synapses: update 1989. 216 9

Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1-100 mumol/l) was applied cumulatively and EC50 and IC50 values measured from individual concentration-response curves. Blockade of 5-HT responses by the 3-indazole carboxamide, BRL 43694, was investigated and compared with the blocking action of metoclopramide. BRL 43694 was a selective antagonist of 5-HT responses. A concentration of 10 nmol/l BRL 43694, which nearly abolished the depolarization and reduction of the C spike evoked by 5-HT (100 mumol/l), had no effect on similar responses evoked by DMPP (100 mumol/l) or GABA (100 mumol/l). Blockade of 5-HT responses by BRL 43694 (0.3 nmol/l) was slow in onset, a plateau blockade occurring after equilibrium of tissue with antagonist for 2 to 3 h. Metoclopramide induced a blockade of rapid onset. The maximal blockade was apparent within 30 min of application. Full recovery in the responsiveness of the tissue to 5-HT was observed within 30 min of washing out metoclopramide. BRL 43694 at concentrations of 0.3, 1, 3 and 10 nmol/l caused a progressive rightward shift of the concentration-response curves to 5-HT. At the highest concentration of antagonist, there was some depression of the maximal 5-HT response. The apparent pA2 estimated from the Schild equation was 10.03 +/- 0.09 (mean +/- SEM, n = 20) against 5-HT depolarization and 10.31 +/- 0.1 against C spike reduction. Schild plots had slopes not significantly different from 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of the effects of 5-hydroxytryptamine on the rabbit isolated vagus nerve by BRL 43694 and metoclopramide. 216 21

Effect of bath application of the inhibitory amino acids (glycine and GABA) on motoneurons of EPSPs was studied in the normal physiological solutions and after preliminary administration of antagonists: strychnine (10(-6) mol/l), bicuculline (10(-4) mol/l) or picrotoxin (10(-4) mol/l). All these antagonists diminished the depression of monosynaptic EPSPs which were elicited by both amino acids (glycine and GABA). Data obtained in this study and previously reported ones permit concluding that motoneuron membranes in the spinal cord of lamprey possess the unit receptor channel complex sensitive to both amino acids.
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PMID:[The effect of glycine and gamma-aminobutyric acid on the excitatory postsynaptic potentials of the spinal motor neurons in the lamprey in the presence of antagonists]. 216 34

1. Whole-cell patch-clamp techniques were used to record the excitatory postsynaptic current (EPSC) in a cultured mouse hippocampal neurone that resulted from electrical stimulation of another neurone in the cell culture. 2. L-Glutamate (less than 1 microM) reversibly depressed the EPSC amplitude in 67% of the synapses tested. The average amplitude reduction was 40%. The depression by glutamate was not blocked by extracellular magnesium (0.8 mM) or 2-amino-5-phosphonovaleric acid (AP5, 100 microM), indicating that N-methyl-D-aspartate (NMDA) receptors were not involved. 3. The phosphonic derivative of glutamate, L-2-amino-4-phosphonobutyrate (L-AP4), also depressed the EPSC amplitude. Neither glutamate nor L-AP4 induced any detectable inward current at concentrations which produced a potent depression of the EPSC. Statistical analysis of the amplitude fluctuations of evoked synaptic currents showed that the depression induced by both glutamate and L-AP4 was due to a decrease in the probability of synaptic release, confirming a presynaptic site of action. 4. Kainate and quisqualate also depressed excitatory synaptic transmission, but this action was related to the postsynaptic inward current that they induced. Statistical analysis showed that this action was consistent with a purely postsynaptic site of action. 5. Paired EPSCs separated by 20 ms showed either depression or potentiation of the second synaptic response. There was a strong correlation between those EPSCs which exhibited paired pulse depression and those depressed by glutamate application. 6. gamma-Aminobutyric acid (GABA) and baclofen also depressed excitatory synaptic transmission. This depression was not blocked by picrotoxin (100 microM). GABA (10 microM) was effective in 85% of cell pairs tested, while baclofen (5 microM) depressed every EPSC tested. A presynaptic site of action for both substances was indicated by the statistical analysis. 7. The results indicate that both glutamate and GABA suppress excitatory synaptic transmission by an action at presynaptic sites. The glutamate-induced depression may result from activation of a distinct excitatory amino acid receptor for which L-AP4 is a specific agonist.
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PMID:Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones. 217 2


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