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)

Sucrose gap techniques recorded dorsal root potentials evoked by supramaximal dorsal root stimulation in in vitro, hemisected frog spinal cords. In 0 mM Mg2+ large (mean 13.0 mV), long lasting (mean 8.1 s) dorsal root potentials were recorded which consisted of two components: (1) an early component sensitive to picrotoxin, bicuculline, and low [Cl-]o and presumably produced by activation of GABAA receptors; and (2) a long-duration second component enhanced and lengthened by picrotoxin, bicuculline and low [Cl-]o and thought to result from increased interneuron discharges resulting from depression of GABA-mediated pre- and postsynaptic inhibition. Both the early and late components were reduced by over 90% in amplitude and duration by 20 mM Mg2+ or by kynurenate and bicuculline. The early component of the dorsal root potential may depend mainly upon activation of non-N-methyl-D-aspartate receptors. Thus, the N-methyl-D-aspartate antagonist D-(-)-2-amino-5- phosphonovalerate caused only a modest reduction in the amplitude of the early dorsal root potential component while the non N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione caused a much more substantial reduction. Exposure of the spinal cord to a "physiological" concentration of Mg2+ (1.0 mM) greatly reduced the duration and somewhat reduced the amplitude of the dorsal root potential. The reduction of dorsal root potentials by 1.0 mM Mg2+ appears to be caused by both pre- and postsynaptic factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dorsal root potentials in the isolated frog spinal cord: amino acid neurotransmitters and magnesium ions. 167 40

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

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.
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PMID:Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey. 168 74

Tardive dyskinesia has been connected with regional reductions of GABA functions in the basal ganglia. In view of the possibility that peptides are involved in neuroleptic-induced dyskinesias substance P and dynorphin A levels were measured in the basal ganglia of the Cebus apella model for tardive dyskinesia. In addition, regional glutamate decarboxylase activities, dopamine, homovanillic acid and dihydroxyphenylacetic acid levels were monitored. A significant dyskinesia-related decrease in glutamate decarboxylase activity was found in the subthalamic nucleus, the medial segment of globus pallidus and the rostral part of substantia nigra in accordance with earlier findings. Cebus monkeys with an intact GABA system (neuroleptic-treated controls without dyskinesia) showed increased levels of substance P and homovanillic acid in the caudate nucleus. The changes were confined to the caudal part of the body of the caudate and the nucleus accumbens. On the other hand, the dyskinetic monkeys, with a defective GABA system, did not demonstrate a similar substance P rise in the caudate or nucleus accumbens, but showed a depression of homovanillic acid levels in the caudal part of the body of the caudate nucleus. Dynorphin A, dopamine and dihydroxyphenylacetic acid showed no dyskinesia-related changes. In conclusion, the difference in glutamate decarboxylase activity between animals developing dyskinetic symptoms vs those who did not, was reflected by regional changes in substance P and homovanillic acid levels.
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PMID:Neuropeptide changes in a primate model (Cebus apella) for tardive dyskinesia. 172 15

A volatile anesthetic-gated current was characterized in patch-clamped cultured postnatal rat hippocampal neurons. In this preparation, the major volatile anesthetics, isoflurane, halothane, and enflurane, open an anion-selective conductance. This volatile anesthetic-gated current exhibits anion selectivity with a chloride-to-acetate permeability ratio of 15, shows outward rectification well described by the constant field equation, and is activated in a dose-dependent fashion with half-maximal response to isoflurane at 0.8 mM (0.032 atm). The current persists in the absence of external Ca2+ and is not blocked by strychnine, a glycine antagonist. However, the gamma-aminobutyric acidA (GABAA) antagonists, bicuculline and picrotoxinin, and the nonspecific anion channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), completely block the response. These observations suggest that volatile anesthetics, like several other general anesthetics such as barbiturates, steroids, and etomidate, have a GABA-mimetic effect on vertebrate central neurons in culture. It is not clear whether this GABAA-gating property is a prerequisite for all general anesthetics. However, under normal physiological conditions of low intracellular Cl-, it is likely that drugs with both direct GABA agonist and GABA modulatory properties will produce overall depression of the central nervous system by increasing the normal inhibitory synaptic influence and by directly hyperpolarizing neurons.
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PMID:Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons. 174 Feb 40

A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporomandibular disorder/myofascial pain patients who were not responsive to occlusal splint, behavioral, and physical therapy. Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic, anxiolytic, muscle relaxant, and sedative properties. Clonazepam appears to be effective when compared to a placebo. However, caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction. Indiscriminate administration of clonazepam may be harmful to the patient.
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PMID:Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study. 181 46

Benzodiazepines are generally well tolerated (compared to barbiturates or antidepressants, their side-effects are milder). They may be used safely, their toxicity is low. Benzodiazepine overdosage may be lethal only if the drug is taken simultaneously with other drugs or alcohol. They act primarily through inhibiting the GABA system, their anxiolytic and sedative effects are of primary importance from the psychiatric aspect. Their classification is based on the difference in their receptor affinity (potency) and kinetics. Derivatives of low, medium and high potency are known. The introduction of high potency benzodiazepines in psychiatry has increased the therapeutic means. The major field of indication of benzodiazepine therapy is DSM-III anxiety disorders and insomnias but they may be successfully used in the treatment of manic conditions, schizophrenia, delirium tremens, clinical conditions accompanied by anxiety-depression, acute restlessness, neuroleptic-induced acute distonias, and akathisias. Even if therapeutic doses are used, tolerance to benzodiazepines may develop after some weeks of therapy. The general withdrawal symptoms are not severe, but the rebound symptoms often hinder the discontinuance of the drug or the reduction of doses. When prescribing benzodiazepines the risk of long-term therapy and the prevention of the development of drug addiction have to be considered.
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PMID:Use of benzodiazepines in psychiatry. 181 22

The analysis of GABA levels in plasma of 28 normal persons and 25 patients with endogenous depression did not show any significant differences between both groups. Neither did we observe any differences in GABA levels in patients treated with antidepressant drugs before and after treatment, during a remission or a depression, in responders or nonresponders to treatment. The study did not indicate any results pointing to a role of gabaergic mechanisms in the pathophysiology of endogenous depression or in the action of tricyclic antidepressant drugs.
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PMID:[GABA levels in the plasma of patients with endogenous depression and during the treatment with thymoleptics]. 182 76

The effects of iontophoretically applying the presumed Purkinje cell inhibitory neurotransmitters, GABA and taurine, were tested on neurons of the cerebellar nuclei in normal and in climbing-fiber-deafferented cerebella. Rats treated with 3-acetylpyridine to totally destroy the inferior olive were used for acute experiments 105-185 days after treatment. In controls, nearly all neuronal firing was dose-dependently depressed by both inhibitory amino acids. The depression in firing for both were antagonized by bicuculline and picrotoxin but not by strychnine while TAG specifically antagonized only responses to taurine. At sufficient doses, bicuculline and TAG induced disinhibitory responses (significant release of neuron discharge) in the absence of applied antagonist. In deafferented animals, the inhibitory efficacy of GABA and taurine were drastically reduced; most of the neurons failed to respond to these amino acids at the same iontophoretic parameters as for the control rats. Moreover, high doses of bicuculline and TAG did not induce any disinhibitory response (no significant increase in discharge rate) in most of the neurons tested. These results clearly demonstrate that climbing fiber deafferentation reduces postsynaptic sensitivity of the cerebellar nuclei neurons for the presumed Purkinje cell inhibitory neurotransmitters.
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PMID:Decreased sensitivity of cerebellar nuclei neurons to GABA and taurine: effects of long-term inferior olive destruction in the rat. 185 Dec 71

gamma-Aminobutyric acid (GABA) can influence conduction in a number of axonal preparations from the peripheral and central nervous system. In the spinal cord, the excitability of primary afferent terminals has long been known to be affected by GABA. Whether conduction in the long fiber tracts of the spinal cord can be similarly modulated is unknown. Since GABA causes a pronounced depression of excitability in preparations of unmyelinated axons, and myelination is incomplete in the neonatal rat, we tested whether GABA can modulate conduction in the dorsal columns of 10-17-day-old rats. Experiments were performed in vitro, on isolated dorsal column segments (n = 18). The extracellular compound action potential evoked by submaximal stimuli was recorded with a glass micropipette positioned 0.5-2.0 mm from a stimulating electrode. At concentrations of 10(-4) - 10(-3) M, GABA decreased excitability, reversibly depressing the compound action potential amplitude, and increasing the latency by 47 +/- 11% and 22 +/- 9% (mean +/- S.E.M., n = 5, 10(-3) M), respectively. These effects were blocked by picrotoxin and mimicked by isoguvacine (10(-4) M), which decreased the compound action potential amplitude by 44 +/- 10% and increased the latency by 9 +/- 4% (n = 5). Lower concentrations of these agents caused a modest increase in excitability. At 10(-5) M, GABA increased the compound action potential amplitude by 14 +/- 2% and decreased the latency by 3 +/- 2% (n = 5). Our results demonstrate that functional GABAA receptors are present in neonatal dorsal columns.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAA receptors modulate axonal conduction in dorsal columns of neonatal rat spinal cord. 185 57


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