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)

1. To see whether long-lasting changes in synaptic efficacy are induced in the developing visual cortex (VC), field potentials evoked by test stimulation given alternatively to each of the optic nerves (ONs) were recorded from VC of kittens ranging in age from 4 to 8 wk. In some experiments, field potentials were recorded simultaneously from the dorsal lateral geniculate nucleus (LGN) in addition to VC. 2. Tetanic stimulation was applied to one of the ONs for 1-60 min at 5 Hz. Homosynaptic potentiation of cortical responses, defined as an increase lasting > 2.5 h in the cortical field potential evoked by test stimulation of the ON that was tetanized, was induced without any changes in LGN responses in 3 of the 12 kittens tested. Heterosynaptic depression, defined as a decrease lasting > 0.5 h in the field potential evoked by stimulation of the ON that was not tetanized, was also induced in two of those three kittens. 3. To elucidate a role of inputs originating from spontaneous activity of retinal ganglion cells in induction of potentiation and depression in the cortex, tetrodotoxin (TTX) was injected into both eyes of 11 kittens. After we confirmed the suppression of retinal activity by TTX, tetanic stimulation was applied to ON. Homosynaptic potentiation of cortical responses was induced in 6 of the 11 kittens, and the ratio of the mean amplitude of posttetanic responses to that of pretetanic responses for the 11 kittens was on average larger than that for the 12 control kittens. Heterosynaptic depression was not observed in any of the 11 kittens. 4. To see a role of postsynaptic activity in induction of potentiation and depression, gamma-aminobutyric acid (GABA) was applied continuously to the VC by an infusion pump in 10 kittens. Tetanic stimulation was given to ON while cortical activities were suppressed by GABA. After recovery of cortical activities, homosynaptic depression was found to be induced in 3 of the 10 kittens, but homosynaptic potentiation was not observed at all. The ratio of amplitude of posttetanic to pretetanic responses at the tetanized side for the 10 kittens was on average smaller than that for the 11 TTX-injected kittens. 5. These results can be accounted for by the modified covariance model in which the relation of postsynaptic activity and direction of changes in synaptic efficacy is formulated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activity-dependent potentiation and depression of visual cortical responses to optic nerve stimulation in kittens. 147 33

Local anaesthetics are responsible for 5 to 10% of all reported adverse reactions to anaesthetic drugs. Adverse effects may be classified as: (a) those associated directly with blocking ion channels in cell membranes, such as cardiovascular and CNS toxicity; (b) those due to other effects of drug or vehicle (mainly peripheral nerve complications); (c) allergic reactions (often a mistaken diagnosis); and (d) mechanical or other effects of technique, such as needle trauma or introduction of infection. Signs and symptoms of CNS toxicity include convulsions, followed by coma and respiratory depression. Convulsions are due to disinhibition of nervous conduction, probably by an action at the gamma-aminobutyric acid (GABA) receptor complex, while depressant effects, which predominate at higher doses, are due to blockade of sodium channels. CNS toxicity is potentiated by hypoxia and hypercapnia, so acute management must minimise these. Cardiovascular toxicity also involves sodium channel blockade, reducing contractility and interfering with conduction. Bupivacaine differs from lidocaine (lignocaine) in the sudden occurrence of dangerous ventricular arrhythmias including fibrillation at subconvulsant doses. Ropivacaine is a newer amide local anaesthetic with toxicity intermediate between these but potency similar to bupivacaine. Neurotoxic complications leading to prolonged deficit after intraspinal administration are uncommon. Causes are multifactorial, and include pH of and additives to preparations. Allergic reactions account for only 1% of untoward reactions, but anaphylactoid collapse can be lifeth-reatening and requires rapid and effective management.
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PMID:Adverse effects of local anaesthetics. 150 66

Increasing doses of the injectable anesthetics etomidate, Saffan, thiopental, ketamine, and xylazine and the vehicles saline and propylene glycol were administered to urethane-anesthetized rats. Their effects in vivo on perforant pathway-evoked field excitatory post-synaptic potentials and population spikes in the hippocampal dentate gyrus were determined. The primary purpose was to ascertain whether these compounds affect hippocampal excitability in a manner consistent with their proposed mechanisms of action. Compared with their respective vehicles, thiopental, etomidate, and xylazine reduced the amplitude of population spikes to single perforant pathway stimulation by 20-30% at the highest doses tested. Xylazine also increased the latency to onset of the population spike. No other effects were observed. Using paired pulse paradigms, it was determined that etomidate produced a dramatic, prolonged reduction in granule cell excitability at interpulse intervals of 10-100 ms. The magnitude of the effect was dose related and was reversible with the discontinuance of administration of the drug. Similar changes occurred with Saffan (althesin) and thiopental. Ketamine produced a small but significant depression in granule cell excitability during intervals of 10-200 ms. Xylazine had no effect. These data corroborate the importance of a prolongation of gamma-aminobutyric acid A-mediated inhibition to the mechanism of actions of etomidate, thiopental, and Saffan at relevant exposure concentrations in vivo.
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PMID:Modification of GABA-mediated inhibition by various injectable anesthetics. 151 87

We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical actometer, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scotophase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist flumazenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing gamma-aminobutyric acid (GABA) as an inhibitory transmitter.
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PMID:Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. 156 63

1. Synaptic transmission between dorsal root afferents and alpha-motoneurones was studied in the in vitro hemisected spinal cord preparation isolated from neonatal rats. 2. Repetitive stimulation of the dorsal roots depressed the monosynaptic reflex recorded from the homologous ventral roots. The depression developed within the first five to six pulses in a stimulus train and stabilized at a plateau-like level for many seconds of stimulation. 3. The magnitude of the reflex depression depended on the stimulation interval and was capable of reducing the reflex to 17% of its undepressed control during 5 Hz stimulus trains. Complete recovery from depression was obtained at stimulation intervals greater than or equal to 30 s. 4. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly after reduction of the activity in polysynaptic pathways by addition of mephenesin to the bathing media. These EPSPs exhibited a prolonged, frequency-dependent synaptic depression. The depression reduced the amplitude of the EPSP to 25% of the undepressed control during 5 Hz stimulus trains, and was alleviated completely at stimulus interval greater than or equal to 60 s. 5. The prolonged EPSP depression was not altered by blockade of glycinergic and type-A gamma-aminobutyric acid (GABAA-ergic) receptors underlying postsynaptic inhibition in the spinal cord. Injection of current steps to motoneurones before and during the prolonged depression revealed similar values of the membrane time constant and input resistance. These excluded changes in the passive properties of the motoneurone membrane as an explanation for the observed synaptic depression. 6. Extracellular recordings of terminal potentials and their accompanying synaptic fields from motor nuclei in the ventrolateral cord revealed that the frequency-dependent depression in the synaptic fields was not preceded by any detectable changes in the amplitude or the shape of the terminal potential, suggesting that the depression cannot be attributed to impairment of action potential invasion to the afferent terminals. 7. Reduction of the basic level of transmitter release in the spinal cord by increasing the Mg2+/Ca2+ ratio of the bathing solution or by application of 2 microM of L(-)baclofen markedly diminished the synaptic potential depression at all the stimulation intervals tested in this study. Recovery from depression was evident for stimulation intervals greater than or equal to 5 s. Under these conditions, short tetanic trains (5 pulses at 25 Hz) revealed a substantial facilitation and potentiation of the EPSPs. 8. We suggest that prolonged depression of synaptic potentials in the neonatal rat reflects decreased transmitter output from the activated afferent terminals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro studies of prolonged synaptic depression in the neonatal rat spinal cord. 159 45

We report here some physiological and pharmacological characteristics of noxious stimuli-induced changes in the hippocampal CA1 pyramidal cell synaptic excitability to field CA3 stimulation. A noxious heat stimulus applied to the left hind paw (LHP) produced a persistent depression of the CA1 population spike (PS) which habituated to a repetition of the stimulus. Interestingly, exposure of the tail to a noxious stimulus following habituation of the LHP produced a depression of the CA1 PS. This finding suggested that persistent depression and habituation are topographically represented. In separate experiments we determined that while the persistent depression of the CA1 population spike was accompanied by, in most cases, a prolonged increase in the amplitude of the CA1 antidromic field potential, there was a concurrent persistent depression and habituation of the CA1 PS and the corresponding apical dendritic field excitatory postsynaptic potential (dfEPSP). This suggested that noxious stimulus-induced CA1 synaptic depression is mediated at the apical dendritic region, perhaps postsynaptically at the dendrites and/or presynaptically on CA3 afferent terminals. Furthermore, atropine sulfate (40 mg/kg ip), which prevented the depression of the CA1 PS, also blocked the depression of dfEPSP when iontophoresed at the apical dendritic recording site. In addition atropine antagonized the depression of the dfEPSP produced by iontophoretic acetylcholine (Ach) but not gamma-aminobutyric acid. However, iontophoretic atropine at the cell body recording site did not prevent the depression of the CA1 PS. These results are consistent with the notion that Ach release in the apical dendrites of CA1 pyramidal cells following a noxious stimulus depresses CA1 synaptic excitability.
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PMID:Responses in the CA1 region of the rat hippocampus to a noxious stimulus. 161 85

Gamma-aminobutyric acid (GABA) levels in platelets were measured in 19 patients with migraine (7 males and 12 females, average age: 36.5 years) and 27 patients with chronic tension-type headache (TH; 9 males and 18 females, average age: 48.9 years). Twenty-one normal healthy volunteers composed the control group (11 males and 10 females, average age 34.9 years). The GABA levels in platelets were determined using high performance liquid chromatography with fluorescent detection (HPLC-FC). The GABA levels in platelets were 30.8 +/- 11.7 pmol/10(9) platelets (mean +/- S.D.) in the patients with migraine, 43.1 +/- 11.8 pmol/10(9) platelets in the patients with TH and 34.7 +/- 8.1 pmol/10(9) platelets in the healthy controls. The platelet GABA levels in the patients with TH were significantly higher than in the migraine patients and the healthy controls (p less than 0.05). The possible role of GABA in headache is discussed. We consider that TH may be a state of neuronal hyperexcitability similar to migraine and that GABA in the platelets of patients during TH attacks may be elevated to counterbalance it. Alternatively, we suggest that the rise of GABA levels in platelets is related to emotional factors, such as depression, in the TH patients. Further studies must be undertaken concerning the relationship between platelet GABA levels and headache.
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PMID:Platelet gamma-aminobutyric acid levels in migraine and tension-type headache. 162 59

Diazepam binding inhibitor (DBI) is a 9-kD polypeptide that was first isolated in 1983 from rat brain by monitoring its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the extracellular domain of the type A receptor for gamma-aminobutyric acid (GABAA receptor) and from the mitochondrial BZD receptor (MBR) located on the outer mitochondrial membrane. In brain, DBI and its two major processing products [DBI 33-50, or octadecaneuropeptide (ODN) and DBI 17-50, or triakontatetraneuropeptide (TTN)] are unevenly distributed in neurons, with the highest concentrations of DBI (10 to 50 microMs) being present in the hypothalamus, amygdala, cerebellum, and discrete areas of the thalamus, hippocampus, and cortex. DBI is also present in specialized glial cells (astroglia and Bergmann glia) and in peripheral tissues. In the periphery, the highest concentration of DBI occurs in cells of the zona glomerulosa and fasciculata of the adrenal cortex and in Leydig cells of the testis; interestingly, these are the same cell types in which MBRs are highly concentrated. Stimulation of MBRs by appropriate ligands (including DBI and TTN) facilitates cholesterol influx into mitochondria and the subsequent formation of pregnenolone, the parent molecule for endogenous steroid production; this facilitation occurs not only in peripheral steroidogenic tissues, but also in glial cells, the steroidogenic cells of the brain. Some of the steroids (pregnenolone sulfate, dehydroepiandrosterone sulfate, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one) produced in brain (neurosteroids) function as potent (with effects in the nanomolar concentration range) positive or negative allosteric modulators of GABAA receptor function. Thus, accumulating evidence suggests that the various neurobiological actions of DBI and its processing products may be attributable to the ability of these peptides either to bind to BZD recognition sites associated with GABAA receptors or to bind to glial cell MBRs and modulate the rate and quality of neurosteroidogenesis. The neurobiological effects of DBI and its processing products in physiological and pathological conditions (hepatic encephlopaty, depression, panic) concentrations may therefore be explained by interactions with different types of BZD recognition site. In addition, recent reports that DBI and some of its fragments inhibit (in nanomolar concentrations) glucose-induced insulin release from pancreatic islets and bind acyl-coenzyme A with high affinity support the hypothesis that DBI isa precursor of biologically active peptides with multiple actions in the brain and in peripheral tissues.
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PMID:Diazepam binding inhibitor (DBI): a peptide with multiple biological actions. 164 40

The neurobehavioral responsivity to peripherally injected muscimol, a gamma-aminobutyric acid-A (GABA-A) agonist, was assessed in infant (14-day-old), weanling (20-day-old) and young adult (53-day-old) outbred male mice. In the first experiment, relatively high doses of muscimol (ranging from 0.05 to 0.40 mg/kg in developing and from 0.50 to 3 mg/kg in adult animals) were found to dose-dependently induced solid catalepsy and ataxia, evaluated 5 times at 20-min intervals. In the second experiment, the GABA agonist was injected in dose ranges which include relatively small concentrations in order to assess its excitatory properties, observable in adults, on rearing and locomotion in developing mice. It appeared that levels of rearing and especially locomotion were enhanced at the low doses (0.025 and 0.050 mg/kg in developing, and 1.3 and 1.9 mg/kg in adult mice) and inhibited at the higher ones (0.150 mg/kg in developing and 1.9 and 2.5 mg/kg in adult mice). This adult-like biphasic action of muscimol in developing mice--excitation at low and depression/sedation at high doses--strongly suggests a full maturation of the GABA-A-related behavioral functions at a period of ontogeny where adult-like locomotion emerges. Given that previous studies have shown that muscimol can biphasically affect behavioral activity in newborn murines as well, it is suggested that GABA-related behavioral functions mature near-monotonically during ontogeny, unlike those related to other major neurotransmitter systems.
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PMID:Adult-like biphasic neurobehavioral changes induced by a GABA-A agonist in infant and weanling mice. 166 Dec 11

Because diazepam binding inhibitor (DBI) and its processing products coexist with gamma-aminobutyric acid (GABA) in several axon terminals, DBI immunoreactivity was measured in the cerebrospinal fluid (CSF) of individuals suffering from various neuropsychiatric disorders, that are believe to be associated with abnormalities of GABAergic transmission. Increased amounts of DBI-like immunoreactivity were found in the CSF of patients suffering from severe depression with a severe anxiety component (Barbaccia, Costa, Ferrero, Guidotti, Roy, Sunderland, Pickar, Paul and Goodwin, 1986). Moreover, the amount of DBI and its processing products was found to be increased in the CSF of patients with hepatic encephalopathy (HE) (Rothstein, McKhann, Guarneri, Barbaccia, Guidotti and Costa, 1989; Guarneri, Berkovich, Guidotti and Costa, 1990). The clinical rating of HE correlated with the extent of the increase in DBI in CSF. Other lines of research suggest that DBI and DBI processing products may be important factors in behavioral adaptation to stress, acting via benzodiazepine (BZD) binding sites, located on mitochondria. DBI and its processing products, ODN and TTN, are present in high concentrations in the hypothalamus and in the amygdala, two areas of the brain that are important in regulating behavioral patterns associated with conflict situations, anxiety and stress. In CSF, the content of DBI changes in association with corticotropin releasing factor (CRF) (Roy, Pickar, Gold, Barbaccia, Guidotti, Costa and Linnoila, 1989). Finally DBI is preferentially concentrated in steroidogenic tissues and cells (adrenal cortical cells, Leydig cells of the testes and glial cells of the brain).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of DBI in brain and its posttranslational processing products in normal and abnormal behavior. 166 69

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