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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed.
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PMID:Caudate stimulation and substantia nigra activity in the rat. 0 37

In rats anesthetized with methoxyflurane, phenytoin (DPH) and medazepam (MDZ) were administered iontophoretically to pyramidal and granule cells discharging spontaneously or being driven by acetylcholine or glutamic acid. The objectives were to determine if: 1) these anticonvulsant agents exert direct effects on the rates of discharge of hippocampal neurons; 2) similarities exist between responses elicited by DPH and MDZ; and 3) pyramidal and granule cells differ in their responsiveness to the drugs. The firing rates of 38% of spontaneously active neurons were reduced by iontophoretic DPH. The incidence of depression by DPH depended upon the pretest discharge rates of the cells. Only 5% of cells with spontaneous rates less than 12/sec were depressed by DPH, but 80% with rates faster than 12/sec were inhibited. MDZ depressed 79% of spontaneously firing neurons regardless of pretest discharge rate. A majority of neurons whose firing rates were facilitated by either acetylcholine or glutamate were depressed by DPH or MDZ ejected iontophoretically. Pyramidal and granule cells responded similarly to putative transmitters, but differentially to the drugs. MDZ depressed a much greater proportion of spontaneously active granule cells then DPH. Phenytoin and MDZ differed with regard to the incidence of depression of spontaneous discharges, inhibition of slow firing cells, the proportion of granule cells depressed, and the duration of effect. These differences may be due to potency and pharmacokinetic factors or dissimilar mechanisms of action when the compounds are applied directly to single neurons.
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PMID:Actions of iontophoretic phenytoin and medazepam on hippocampal neurons. 1 97

The possible role of glutamate dehydrogenase, glutamate synthase, and glutamine synthetase in the regulation of enzyme formation in the gamma-aminobutyric acid (GABA) catabolic pathway of Escherichia coli K-12 was investigated. Evidence is presented indicating that glutamine synthetase acts as a positive regulator in the E. coli GABA control system. Mutations impairing glutamate synthase activity prevent the depression of the enzymes of the GABA pathway in ammonia-limited glucose media. However, mutations resulting in constitutive synthesis of glutamine synthetase (GlnC) restore the ability of the glutamate synthase-less mutants to grow in glucose-GABA media and result in depressed synthesis of the GABA enzymes. It is suggested that the loss of glutamate synthesis activity affects the GABA control system indirectly by lowering glutamine synthetase levels.
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PMID:Regulation of gamma-aminobutyric acid degradation in Escherichia coli by nitrogen metabolism enzymes. 2 37

1. In the posterior half of the pulvinar of cats anaesthetized with halothane and nitrous oxide, the majority of neurons were fired by ACh released with small electrophoretic currents. In the anterior part of that nucleus, ACh had more variable effects: excitation, depression or none. 2. In comparison with L-glutamate, DL-homocysteic acid and DL-aspartic acid, ACh appeared to be the most potent excitant. 3. ACh-induced discharges were easily and reversibly blocked by low doses of atropine. In most cases, ACh effects could not be blocked selectively by mecamylamine or dihydro-beta-erythroidine. 4. Nicotine failed to mimic ACh, whereas carbachol was a potent excitant and was readily blocked by low doses of atropine. 5. The histochemical reaction to acetylcholinesterase was moderate in the pulvinar. 6. These observations support the view that pulvinar cells differ from other thalamic cells.
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PMID:Micro-electrophoretic studies in the cat pulvinar region: effect of acetylcholine. 2 59

Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.
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PMID:Neuropharmacology of sedatives and anxiolytics. 3 29

The responsiveness of phasically active brainstem respiratory neurons to several amino acids was investigated in cats under Dial anesthesia. Four-barreled microelectrodes were used to extrude iontophoretically the putative neurotransmitters L-glutamate, L-asparatate, glycine, and gamma-aminobutyric acid (GABA), L-glutamate and L-aspartate caused increased activity when applied to either inspiratory or expiratory neurons and appeared to be equal in efficacy. Likewise, GABA and glycine depressed ongoing phasic neural activity of both inspiratory and expiratory units. In this case, however, the dosage of GABA required to produce a given depression was significantly less than the required dosage of glycine. These findings support the hypothesis that L-glutamate and/or L-aspartate may act as excitatory neurotransmitter agents at the synapses of brainstem respiratory neurons and conversely, GABA may act as the natural inhibitory neurotransmitter.
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PMID:Effects of excitatory and inhibitory amino acids on phasic respiratory neurons. 3 45

The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
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PMID:A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism. 4 Jun 77

Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5--30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude. Smaller doses (less than 5 nA, 0.1 M solution or 20--50 nA, 20 mM in 0.16 M NaCl) reduced the excitation produced by glutamate, aspartate, and homocysteate, but antagonism of acetylcholine-evoked excitations required large flurazepam doses (up to 30 nA, 0.1 M solution). Even lower doses of flurazepam (less than 10 nA, 20 mM in 0.16 M NaCl) enhanced the inhibitory effect of gamma-aminobutyric acid (GABA) but antagonized that of 5-hydroxytryptamine, and had no effect on dopamine-induced inhibition of firing. Hence, only GABA-evoked inhibitions were significantly potentiated by flurazepam. These results demonstrate the multiple possible interactions between a benzodiazepine and different putative neurotransmitters in the mammalian cerebral cortex.
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PMID:Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters. 4 77

1. Bath-application of L-glutamate to crayfish opener muscle causes depolarization and resistance changes which both increase with falling temperature. At temperatures above 15 degrees C there is usually a resistance increase, at lower temperatures the resistance is decreased. 2. Meso-gamma . gamma'-diaminosuberic acid-dihydrochloride (meso-di-GABA) and dl-diamino-nonanedicarboxylic acid dihydrochloride (C-9) were newly synthesized as potential glutamate blockers. 3. Meso-di-GABA (10(-4) to 10(-3)M) usually caused a significant increase (15 degrees C) or decrease (7 degrees C) of membrane resistance and slight depolarization. Excitatory junction potentials (ejps) were reversibly depressed or blocked while the effects of glutamate were potentiated. The depression or block of neuromuscular transmission was not prevented by picrotoxin or by concanavaline A. 4. C-9 (3 x 10(-4) M) depressed or blocked the effect of applied glutamate with little or no effect on ejps. 5. The results are best explained by assuming that bath-applied glutamate acts mainly on extrasynaptic receptors. Meso-di-GABA is assumed to block synaptic receptors and to activate non-synaptic receptors while C-9 seems to act mainly as a blocker of glutamate action on non-synaptic receptors.
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PMID:Is glutamate the transmitter of crustacean motoneurons? 4 27

Chronic ammonia toxicity in experimental mice was induced by exposing them for 2 and 5 days to 5 % (v/v) ammonia solution. The enzymes concerned with glutamate metabolism (aspartate-, alanine- and tyrosine aminotransferases, glutamate dehydrogenase and glutamine synthetase) and (Na+ + K+)-ATPase were estimated in the three regions of brain (cerebellum, cerebral cortex and brain stem) and in liver. Glutamate, aspartate, alanine, glutamine and GABA, RNA and protein were also estimated in the three regions of brain and liver. A significant rise in the activity of (Na+ + K+)-ATPase in all the three regions of brain along with a fall in the activity of alanine aminotransferase was noticed. Changes in the activities of other enzymes were also observed. A significant increase in alanine and a decrease in glutamic acid was observed while no change was observed in the content of other amino acids belonging to the glutamate family. As a result of this, changes in the ratios of glutamate/glutamine and glutamate + aspartate/GABA was observed. The results indicated that the brain was in a state of more depression and less of excitation. Under these conditions the liver tissue was showing a profound rise in the activity of the enzymes of glutamate metabolism. The results are further discussed.
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PMID:Chronic metabolic effects of ammonia in mouse brain. 9 19


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