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)

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

The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism.
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PMID:Comparison of gabapentin with other antiepileptic and GABAergic drugs. 186 22

Ionol, a synthetic antioxidant, limits the stressor liver injury to a greater extent than sodium, valproate and phenazepam, activators of a GABA-ergic link of the stress-limiting organism systems. This injury is exhibited in the organospecific elevated levels of blood enzymes fructosediphosphate aldolase depression of N-demethylase activity of microsomal monooxygenases and a decrease in the amount of cytochromes P-450 and B5.
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PMID:[Comparative evaluation of the protective effect of sodium valproate, phenazepam and ionol in stress-induced liver damage in rats]. 189 54

Little is known about possible hypothalamic modulation of the respiratory response to baroreceptor activation. The purpose of this study was to determine if the respiratory depression associated with the baroreceptor reflex is modulated by neurons in the posterior hypothalamus. Breathing frequency and tidal diaphragmatic activity were derived from diaphragmatic electromyographic recordings in anesthetized rats. Respiratory responses to baroreceptor activation were analyzed before and after unilateral microinjections of GABA antagonists (picrotoxin, bicuculline methiodide) or a GABA synthesis inhibitor (3-mercaptopropionic acid, 3-MP) into the posterior hypothalamus. Baroreceptor stimulation prior to microinjections elicited a decrease in both breathing frequency and tidal diaphragmatic activity. Microinjection of picrotoxin elicited an increase in respiratory activity. The decrease in tidal diaphragmatic activity evoked by baroreceptor stimulation was blocked after the microinjection. Furthermore, the baroreceptor-induced fall in breathing frequency was converted to an increase in breathing frequency. These effects of picrotoxin were reversed by microinjections of a GABA agonist (muscimol) into the same site. Microinjections of 3-MP also blocked the decrease in breathing frequency associated with baroreceptor stimulation. The GABA antagonist bicuculline methiodide elicited similar effects. These results indicate that a GABAergic mechanism in the posterior hypothalamus modulates the respiratory responses to baroreceptor stimulation.
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PMID:Hypothalamic GABAergic modulation of respiratory responses to baroreceptor stimulation. 196 95

The involvement of GABAergic systems in the pathogenesis of HE was supported by electrophysiologic studies of single Purkinje neurons from rabbits with HE which demonstrated the hypersensitivity of these neurons to depression by GABA and BZ receptor agonists. In contrast, these neurons were excited by BZ receptor antagonists. At concentrations which had no effect on neuronal activity, BZ receptor antagonists also reversed the hypersensitivity of HE neurons to depression by muscimol. This combination of neuronal responses is consistent with an increase in the concentration or availability of a ligand for the BZ receptor with agonist properties in the brains of rabbits with HE. Subsequent neurochemical studies support these electrophysiologic observations. Autoradiographic techniques indicated the presence of a reversible inhibitor of [3H]Ro 15-1788 and [3H]flunitrazepam binding to the cerebral and cerebellar cortices of rabbits with HE. The ability of this substance to inhibit [3H]flunitrazepam binding to HE rabbit brain sections was further enhanced in the presence of NaCl and GABA. The autoradiographic studies suggested that the density and affinity of the components of the GABA-BZ receptor complex are unaltered in this animal model of HE. This inference is fully supported by the subsequent studies of radioligand binding to well-washed membrane preparations. Finally, extracts of HE rabbit brains yielded a family of substances with the properties of BZ receptor agonists. These substances may include, but are not limited to, diazepam, oxazepam and desmethyldiazepam, but do not include substances commonly elevated in the plasma and CSF of patients with HE4. The positive identification of these substances awaits confirmation by mass-spectroscopic analysis. However, the precedent for the presence of a family of benzodiazepines in animals that were not administered these drugs has been set. The origin of these substances is a matter of ongoing research. Several studies have shown the presence of benzodiazepines in plant and animal materials. It is possible that these "endogenous" benzodiazepines are the result of contamination of the food chain. A normally functioning liver would capture and metabolize these compounds after their absorption from the gut. This function of the liver would be impaired in liver failure, thus allowing sufficient levels of BZ receptor agonists to accumulate in the CNS, contributing to the pathogenesis of HE. However, studies by DeBlas and coworkers have reported that 1,4 benzodiazepines are present in human brains preserved prior to the commercial use of these compounds. Further, they have found benzodiazepines in cell lines cultured without potential exogenous sources of benzodiazepines.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of the benzodiazepine receptor in hepatic encephalopathy: evidence for the presence of a benzodiazepine receptor ligand. 196 66

The binding of the triazolobenzodiazepine [3H]alprazolam was studied to characterize the in vitro interactions with benzodiazepine receptors in membrane preparations of rat brain. Studies using nonequilibrium and equilibrium binding conditions for [3H]alprazolam resulted in high specific to nonspecific (signal to noise) binding ratios. The binding of [3H]alprazolam was saturable and specific with a low nanomolar affinity for benzodiazepine receptors in the rat brain. The Kd was 4.6 nM and the Bmax was 2.6 pmol/mg protein. GABA enhanced [3H]alprazolam binding while several benzodiazepine receptor ligands were competitive inhibitors of this drug. Compounds that bind to other receptor sites had a very weak or negligible effect on [3H]alprazolam binding. Alprazolam, an agent used as an anxiolytic and in the treatment of depression, acts in vitro as a selective and specific ligand for benzodiazepine receptors in the rat brain. The biochemical binding profile does not appear to account for the unique therapeutic properties which distinguish this compound from the other benzodiazepines in its class.
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PMID:Characterization of [3H]alprazolam binding to central benzodiazepine receptors. 196 24

The present study reports that long-term (18 days) administration of imipramine (IMI, 20 mg/kg) or desipramine (DMI, 15 mg/kg) produced a significant decrease in the GABA-stimulated 36Cl- uptake into membrane vesicles from the cerebral cortex of rats (experiment 1). Experiments 2A, B show that anti-immobility effects of DMI and IMI (subacute treatment) in the forced swimming test are enhanced when a single subconvulsant injection of picrotoxin or pentylenetetrazol is administered to the animals concurrently to the last antidepressant injection. These results are discussed in relation with a current GABAergic hypothesis of depression and antidepressant drug action.
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PMID:Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats. 196 14

In order to test the functional significance of rapid eye movement (REM)-sleep and noradrenergic activity for cerebral cortex maturation, rat pups were daily injected with clonidine from 8 to 21 days of life. Previous studies have shown that this treatment reduces the amount of time spent in REM-sleep and the level of noradrenaline turnover in the brain. For long-term consequences of such treatment in adulthood, cortical neuron responses to micro-iontophoretically applied neurotransmitters were studied. No significant differences were found in the single cell responses to glutamate, GABA or noradrenaline in the cerebral cortex of clonidine treated rats as compared with age matched controls. However, the magnitude of GABAergic depression of glutamate induced neuronal responses was greater in the clonidine than in the control group.
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PMID:Cortical neuron sensitivity to neurotransmitters following neonatal noradrenaline depletion. 197 Feb 21

A number of studies have shown significant interactions between neuronal systems involved with corticotropin-releasing factor (CRF) and either the clinical manifestations of depression and anxiety or the effects of antidepressant or anxiolytic drugs. In the present study, effects of CRF were studied alone and in combination with imipramine and with the sedative-hypnotic/anxiolytic drugs pentobarbital and chlordiazepoxide. Interactions of CRF with the novel, atypical anxiolytic buspirone were also examined. Interactions were evaluated through the use of schedule-controlled responding, responding suppressed by punishment, and drug discrimination procedures using the conditioned key-pecking response of pigeons. Effects of CRF were significantly enhanced when given in combination with imipramine with low noneffective imipramine doses potentiating the rate-reducing effects of CRF. Similarly, in pigeons trained to discriminate imipramine from saline, noneffective doses of CRF shifted the imipramine dose-response curve more than twofold to the left. Low doses of imipramine that produced saline key responding, produced imipramine-key responding when coadministered with CRF. The CRF antagonist alpha-helical CRF9-41 did not alter the rate-decreasing effects of imipramine. Effects of CRF on schedule-controlled responding were, however, antagonized by the administration of chlordiazepoxide and pentobarbital but not by buspirone, suggesting that CRF interacts with the GABA/benzodiazepine receptor mechanism complex but not with those systems involved in mediating the effects of buspirone. These results suggest that CRF interacts in significant ways with specific neurotransmitter systems subserving depression and anxiety.
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PMID:Interactions of corticotropin-releasing factor with antidepressant and anxiolytic drugs: behavioral studies with pigeons. 197 Jul 44

Meige's disease is a form of focal dystonia characterized by symmetric dystonic spasms of facial muscles, sometimes associated with dystonic movements of other midline muscle groups. The etiology and pathophysiology of the disease have not been established. There is evidence that Meige's disease may result from striatal dopaminergic preponderance coupled with cholinergic overactivity. Several authors have noted a high prevalence of depression in patients with Meige's disease, suggesting a common neurochemical abnormality. Depression, in turn, is associated with decreased pineal melatonin secretion. We propose, based on studies demonstrating that melatonin regulates dopaminergic, cholinergic and GABA-ergic functions, that alterations in melatonin functions may enhance the development of the disease. This hypothesis may open new avenues toward understanding the pathophysiology of the disease and developing newer therapeutic strategies.
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PMID:Melatonin secretion and the pathophysiology of Meige's disease (idiopathic orofacial dystonia): a hypothesis. 197 65


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