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. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro-electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration-response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non-competitive manner to antagonize the GABA-induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be -23.5 plus or minys 6.1 mV. EGABA was independent upon [cl-]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, Bf4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO-3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. 9. The ten anions larger than ClO3- produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3-, indicated that this depression was non-competitive.
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PMID:Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones. 63 14

Bicuculline methochloride (BMC), applied by microiontophoresis, tends to depolarize spinal motoneurons and lower their input resistance. With approximately equal iontophoretic currents of gamma-aminobutyric acid (GABA) and BMC, there is an almost equal chance of observing no change, a potentiation, or a depression of the GABA-evoked conductance increase. A block of the GABA action is seen consistently only when the iontophoretic current of BMC is at least double that of GABA. Under these conditions BMC can selectively antagonize GABA without blocking the effects of glycine, though the latter can also be blocked by larger amounts of BMC. BMC also regularly eliminates the usual apparent desensitization to GABA. This may be due to depression of GABA uptake by BMC, which would also account for its potentiating action at lower relative doses. Comparable effects are observed with iontophoretic applications of benzyl penicillin (BP); but even large doses of BP produce no definite change in membrane properties or in conductance increase evoked by GABA or glycine.
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PMID:Bicuculline, benzyl penicillin, and inhibitory amino acids in the spinal cord of the cat. 88 20

The AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA receptor antagonist 2-amino-5-phosphonovalerate (D-APV) were used to investigate the contribution of excitatory amino acid (EAA) receptors to graded bursting activity recorded in the CA1 region of the rat hippocampal slice following bath application of the convulsant drug bicuculline methiodide (BIC, 2-3 microM). CNQX (5-9 microM) significantly antagonised the burst in a reversible, concentration-dependent manner (n = 5). The effect involved a reduction in the amplitude but not the number of population spikes of the burst and also a depression of the underlying burst excitatory post-synaptic potential (EPSP). D-APV (5-25 microM), in contrast, reduced the amplitude and number of spikes in the burst but had no effect on the burst EPSP (n = 5). Following a single concentration of CNQX (5 microM), applied in the presence of bicuculline, it was observed that the components of epileptiform response which remained could be completely abolished with D-APV (10 microM; n = 10). It was also shown that, following elimination of synaptic transmission with CNQX (5 microM), application of bicuculline (2-3 microM) induced a small burst that could be reversibly antagonised with D-APV (10 microM). These results show that evoked epileptiform activity witnessed in the presence of bicuculline involves the activation of both AMPA and NMDA receptors, the AMPA receptor activation making the major contribution. The burst mediated by NMDA receptors is not dependent on prior activation of AMPA receptors.
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PMID:The contribution of AMPA and NMDA receptors to graded bursting activity in the hippocampal CA1 region in an acute in vitro model of epilepsy. 135 60

The interaction between the GABAA receptor antagonist bicuculline and the benzodiazepine receptor (BR) antagonist flumazenil was studied in the lumbosacral cord of spinal cats. Bicuculline (0.8 mg/kg i.v.) evoked epileptiform bursting of motoneurons in parallel with a depression of peripherally elicited dorsal root potentials (DRP) and dorsal root reflexes (DDR). A low dose of flumazenil (0.03 mg/kg i.v.) reduced the bursting activity of motoneurons as well as partially reversed the depression of DRP and DRR induced by bicuculline. It is suggested that an endogenous BR ligand down-regulating GABAA receptors is released during the bicuculline-evoked enhancement of neuronal activity and may contribute to the epileptiform discharge of motoneurons in the spinal cord.
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PMID:Benzodiazepine antagonist flumazenil reduces bicuculline-induced enhancement of neuronal activity in the spinal cord. 164 18

The interaction between ethanol and cysteine sulfinic acid was examined in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measurement of central nervous system depression. In addition, the interaction between ethanol and cysteic acid, a metabolite of cysteine sulfinic acid, was studied. Immediately after the animals regained the righting reflex following ethanol injection (IP), mice were given an ICV injection of saline, cysteine sulfinic acid (1, 15 or 25 mumol/kg) or cysteic acid (1, 15, or 25 mumol/kg). There occurred a return to the LORR within 30 s after the ICV injection of drugs. The return to the LORR by the administration of the amino acids in the presence of ethanol occurred in a dose-dependent fashion. When cysteine sulfinic acid or cysteic acid (25 mumol/kg, ICV) was injected in the absence of ethanol, no loss of the righting reflex occurred. In other experiments, bicuculline methiodide was given ICV with cysteine sulfinic acid (25 mumol/kg), cysteic acid (25 mumol/kg), or GABA (25 mumol/kg) in the presence of ethanol. Bicuculline methiodide, a GABA antagonist, reduced the effects of the three amino acids to produce a return to the LORR in the presence of ethanol. These results indicate that cysteine sulfinic acid, an excitatory amino acid, and cysteic acid can enhance the central depressant properties of ethanol. Since bicuculline antagonized the effects of these two amino acids, a GABAergic mechanism may be involved in the interaction between ethanol and cysteine sulfinic acid or cysteic acid.
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PMID:Cysteine sulfinic acid can enhance the central depressant effect of ethanol in mice. 168 2

The effects of two general anaesthetics, isoflurane--a volatile agent, and Althesin--a steroid preparation, were studied on the membrane electrical properties and spike activities of 64 neurons in in vitro slice preparations of neocortex excised from anterior cingulate and sensorimotor areas of guinea-pig brain. Spontaneous activity was depressed, and the thresholds for spikes evoked by intracellular injections of current pulses were increased in most neurons during applications of isoflurane in clinical concentrations (0.5-2.5 minimum alveolar concentration or MAC) and Althesin (15-100 microM). The MAC values are equivalent to 1-4% isoflurane in the gaseous phase. Applications in the higher ranges (1.5-2.5 MAC and 300-1500 microM) usually induced a small hyperpolarization (range, 3-8 mV) and an increase (10-30%) in input conductance. The repetitive spike firing evoked by current-pulse injections was inhibited and not uncommonly, abolished completely by an anaesthetic application. A striking feature in the actions of both agents on all neurons was the dose-dependent, reversible depression in amplitude and duration of the postspike afterhyperpolarizations (AHPs). These effects could not be attributed to anaesthetic induced changes in resting potentials, input conductances, or to the reduced number of evoked spikes. Bicuculline (50 microM) was applied concomitantly in 8 neurons with the anaesthetics to block Cl-conductances mediated by GABA-receptors that otherwise may "contaminate" the AHPs. In the presence of bicuculline, both anaesthetics produced a greater reduction in the amplitude and duration of the AHPs which are generated through Ca2+-mediated K+-conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postsynaptic depression induced by isoflurane and Althesin in neocortical neurons. 254 75

The laminar distribution of gamma-aminobutyric acid (GABA) in the superior colliculus of the guinea pig was analyzed. The superficial gray layer, especially the upper half, was found to contain the highest amount, 37.4 +/- 1.1 mmol/kg dry. To investigate the role of GABA in the superficial gray layer, the effect of GABA on neurotransmission in the superficial gray layer was studied in superior colliculus slices in a perfusion system. Bath-applied GABA, 100 microM-1 mM, enhanced the amplitude of the postsynaptic field potential (PSP) in the superficial gray layer dose dependently and at concentrations above 1 mM it depressed the PSP dose dependently. A similar response pattern was obtained with muscimol (0.1-10 microM, enhancement; greater than 10 microM, depression). However, (-)-baclofen only inhibited the PSP dose dependently (0.1-1 microM). The excitatory effect of GABA was enhanced at concentrations of nipecotic acid less than 0.5 mM. Bicuculline 1 microM shifted the dose-response curve of GABA to the right and the excitatory effect was also enhanced. These results indicate that GABA has a dual action on neurotransmission in the superficial gray layer: an excitatory effect, possibly mediated by GABAA receptors and an inhibitory effect mediated by both GABAA and GABAB receptors.
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PMID:Excitatory and inhibitory action of GABA on synaptic transmission in slices of guinea pig superior colliculus. 285 12

The effects of clonidine on the antianxiety and sedation of benzodiazepines (BZD) were assessed respectively in rats trained in a two-lever diazepam cue discrimination procedure and in single-lever fixed-ratio (FR) water-reinforced performance. Clonidine (10-60 micrograms/kg) significantly shifted to the left the dose-effect curves of diazepam in the discrimination paradigm. This treatment also shifted generalization dose-effect curves of the diazepam cue to chlordiazepoxide and CL 218,872 to the left in the drug discrimination procedure. The diazepam cue was antagonized in a dose-related manner by Ro 15-1788, but not by bicuculline. Clonidine also potentiated the rate-decreasing effects of diazepam on the FR schedule when the dose of diazepam was increased to 0.3 mg/kg, but not the milder rate-decreasing effect of CL 218,872 until the dose of CL 218,872 was increased to 10 mg/kg. The potentiating effects of clonidine on the stimulus control and depression of diazepam were antagonized by yohimbine. Yohimbine (1.0 mg/kg) also significantly shifted the dose-effect curve of diazepam cue to the right. Bicuculline (3 mg/kg) completely antagonized the rate-decreasing effect of diazepam (1 mg/kg), but significantly potentiated the rate-suppressant effect of clonidine (10 micrograms/kg). These results suggest that the central noradrenaline (NA) system may be involved not only in the antianxiety, but also the sadative action of BZD. The nature of NA involvement in relation to the different subtypes of BZD receptors requires further exploration.
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PMID:Behavioral evidence for the role of noradrenaline in putative anxiolytic and sedative effects of benzodiazepines. 290 Nov 23

The depressing effect of GABA on excitation of nerve cells as well as the action of bicuculline, penicillin and thiopental on this process were examined on CA1 pyramidal neurons using rat hippocampal slices. It was found that GABA effectively and reversibly reduced the amplitude of antidromic population spike both in the region of somata and dendrites. The sensitivity of apical dendrites to GABA was greater by one order than that of somata, increasing along dendrites from their proximal to distal parts. The somata of pyramidal neurons showed strong desensitization to GABA. In distal parts of dendrites desensitization to GABA was absent. Bicuculline and penicillin antagonized the action of GABA at all investigated levels of CA1 pyramidal cells. Bicuculline blocked the effect of GABA on the somata and dendrites approximately equally. The antagonistic action of penicillin was 10 times larger in the pyramidal layer than in the region of dendrites. Thiopental intensified the depression produced by GABA. Potentiating effect of thiopental was stronger in dendrites. It is concluded that the membrane of CA1 pyramidal neurons has two types of bicuculline-sensitive GABA-receptors differing in their location (mainly on the soma or dendrites), in pharmacology and in ability to be desensitized by GABA.
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PMID:[Sensitivity to GABA of the soma and dendrites of pyramidal cells in isolated sections of hippocampus in the rat]. 300 93

A functional differentiation of the respiratory action of pentobarbital was made by applying the drug in cats to the ventral surface of the medulla and to the dorso-rostral surface of the pons. The involvement of a GABAergic mechanism was assessed by studying the interaction of bicuculline with pentobarbital at both levels of the brain-stem. In the medulla, pentobarbital (4 to 16 mg) caused an immediate and dose-dependent depression of tidal volume down to apnea with a minimal or no change in frequency. In the pons, the depression affected selectively the frequency (-45%) without modification in amplitude. Medullary structures were much more sensitive to the action of pentobarbital. Doses that induced apnea in the medulla did not attain 50% depression of the minute volume in the pons. Bicuculline (300 micrograms) completely antagonized the effect of pentobarbital in both regions, suggesting that a GABAergic mechanism may be involved in the respiratory action of pentobarbital.
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PMID:Mechanism of the respiratory action of pentobarbital at the medullary and pontine levels. 301 25


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