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)

Methamphetamine (METH) is a major drug of abuse which causes neurotoxicity by depleting dopamine, its metabolites, high-affinity dopamine uptake sites and tyrosine hydroxylase activity in the striatum. Dopamine depletion and reduced dopamine transit are associated with depression. S-Adenosylmethionine (SAM) is the chief methyl donor used in dopamine and other neurotransmitter metabolism in mammals. Low SAM is associated with depression and other psychological and neurological disorders in humans. SAM is used to treat depression and some other neurological and psychiatric disorders. The present study was designed to determine if single or multiple doses of METH induce alterations in blood or liver SAM in mice and if these correlate with dopamine levels in the striatum. Adult male C57 mice were injected intraperitoneally with either single (1 x 40 mg/kg) or multiple (4 x 10 mg/kg) doses of METH. Animals were sacrificed at various intervals. A single injection of METH resulted in slightly higher blood SAM levels at 4 hr. Multiple doses of METH resulted in decreased hepatic and blood SAM levels at 72 hr. Blood SAM returned to control levels by 1 wk. Published work shows that dopamine levels increase hours after a single injection of METH, whereas dopamine decreases days after multiple injections of METH. These present data clearly demonstrate that METH dosing leads to significant alterations in liver and blood SAM and that these changes in SAM levels correlate with changes in striatal dopamine levels.
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PMID:Methamphetamine treatment affects blood and liver S-adenosylmethionine (SAM) in mice. Correlation with dopamine depletion in the striatum. 966 77

This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.
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PMID:Depression in the medical setting: biopsychological interactions and treatment considerations. 1008 82

Alterations in catecholamine levels and neurotransmission have been shown in depressive disorders. However, the exact sites of alterations and the relation between these alterations to the etiology of the disease and the effectiveness of antidepressant therapy are poorly understood. In this study, catecholamine levels and metabolism were measured in specific brain regions of a genetic rat model of depression [Flinders Sensitive Line (FSL) rats], and compared to normal Sprague-Dawley rats. Norepinephrine levels were found to be two to threefold higher in the nucleus accumbens, prefrontal cortex, hippocampus and median raphe nucleus of FSL rats as compared with control Sprague-Dawley rats. Dopamine levels were sixfold higher in the nucleus accumbens and twofold higher in the striatum, hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley rats. After chronic treatment with the antidepressant desipramine, the immobility score in a swim test, as a measure of a behavioral deficit, as well as catecholamine levels of the FSL rats became normalized, but these parameters in the control rats did not change. The results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased catecholamine levels in specific brain sites, and further suggest the FSL rats as a model for elucidation of the molecular mechanism of clinically used antidepressant drugs.
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PMID:Increased catecholamine levels in specific brain regions of a rat model of depression: normalization by chronic antidepressant treatment. 1019 55

Dopamine, acting at a D1-like receptor, depresses the release of glutamate in the nucleus accumbens (NAcc) in brain slices, thereby reducing the amplitude of the excitatory postsynaptic current (EPSC). This effect depends upon an inhibitory feedback action of adenosine, liberated following facilitation of postsynaptic NMDA receptors by D1 receptor activation, an action independent of adenylyl cyclase stimulation or cyclic AMP-dependent protein kinase (PKA; Harvey, J., Lacey, M.G., 1997. J. Neurosci. 17, 5271). Using whole-cell recording from NAcc neurones, the dopamine depression of the EPSC was blocked by pre-treatment of brain slices with the selective protein kinase C (PKC) inhibitor Ro 32-0432, but only minimally attenuated by intracellular dialysis of single cells with Ro 32-0432 in the recording pipette. With synaptic transmission blocked by tetrodotoxin, inward currents caused by application of NMDA were enhanced by the D1 receptor agonist SKF 81297A in half the cells tested. In a separate population of cells dialysed intracellularly with Ro 32-0432, SKF 81297A was without effect on NMDA current amplitude. These findings indicate a functional role for phospholipase C-coupled D1-like receptors in both modulating synaptic transmission in NAcc and potentiating NMDA receptors on a subset of NAcc neurones, via PKC activation.
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PMID:Modulation by dopamine D1-like receptors of synaptic transmission and NMDA receptors in rat nucleus accumbens is attenuated by the protein kinase C inhibitor Ro 32-0432. 1021 63

Dopamine is found in both neuronal and non-neuronal tissues in the larval stage of the fruit fly, Drosophila melanogaster, and functions as a signaling molecule in the nervous system. Although dopaminergic neurons in the central nervous system (CNS) were previously thought solely to be interneurons, recent studies suggest that dopamine may also act as a neuromodulator in humoral pathways. We examined both application of dopamine on intact larval CNS-segmental preparations and isolated neuromuscular junctions (NMJs). Dopamine rapidly decreased the rhythmicity of the CNS motor activity. Application of dopamine on neuromuscular preparations of the segmental muscles 6 and 7 resulted in a dose-responsive decrease in the excitatory junction potentials (EJPs). With the use of focal, macro-patch synaptic current recordings the quantal evoked transmission showed a depression of vesicular release at concentrations of 10 microM. Higher concentrations (1 mM) produced a rapid decrement in evoked vesicular release. Dopamine did not alter the shape of the spontaneous synaptic currents, suggesting that dopamine does not alter the postsynaptic muscle fiber receptiveness to the glutaminergic motor nerve transmission. The effects are presynaptic in causing a reduction in the number of vesicles that are stimulated to be released due to neural activity.
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PMID:Dopaminergic modulation of motor neuron activity and neuromuscular function in Drosophila melanogaster. 1032 10

To examine changes in corticostriatal synaptic transmission in rats with ethanol withdrawal syndrome, intracellular and extracellular responses to subcortical white matter stimulation were recorded in neostriatal slice preparations. The resting membrane potential, input resistance and depolarizing postsynaptic potentials to single cortical white matter stimulation were similar in the neostriatum of naive and ethanol withdrawal rats. Repetitive stimulation of the white matter induced more pronounced N-methyl-D-aspartate receptor-mediated postsynaptic potentials in ethanol withdrawal than naive rat neostriatum. In intracellular recording, tetanic stimulation (50 Hz, 20 s) induced more pronounced post-tetanic potentiation of depolarizing postsynaptic potentials in the neostriatum of ethanol withdrawal than naive rats. However, in extracellular recording, tetanic stimulation induced smaller post-tetanic depression of population spikes in the neostriatum of ethanol withdrawal than naive rats. Tetanic stimulation of the subcortical white matter induced long-term potentiation of postsynaptic potentials and population spikes in the ethanol withdrawal rat neostriatum, while long-term depression was evoked in the naive rat neostriatum. The induction of long-term potentiation was blocked by D-2-amino-5-phosphonovaleric acid or 7-chlorokynurenic acid, N-methyl-D-aspartate receptor antagonists, but not by (RS)-methyl-4-carboxyphenyl-glycine, a metabotropic glutamate receptor antagonist. Dopamine also significantly depressed the induction of long-term potentiation in ethanol withdrawal rat neostriatum and this depressant effect was antagonized by the D2 antagonist L-sulpiride but not by the D1 antagonist SCH23390. These results indicate that the N-methyl-D-aspartate component of the corticostriatal glutamatergic responses, which might be necessary for induction of long-term potentiation, was enhanced in ethanol withdrawal rats. The depression of long-term potentiation induction by activation of D2 receptor suggests that corticostriatal N-methyl-D-aspartate response or intracellular mechanisms involving in the induction of the long-term potentiation can be suppressed by D2 activation and that the D2 effects are inhibited in the neostriatum of ethanol withdrawal rats.
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PMID:Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation in the neostriatal neurons in an in vitro slice after ethanol withdrawal of the rat. 1033 60

The cellular and synaptic mechanisms by which general anesthetics affect cell-cell communications in the nervous system remain poorly defined. In this study, we sought to determine how clinically relevant concentrations of sevoflurane affected inhibitory synaptic transmission between identified Lymnaea neurons in vitro. Inhibitory synapses were reconstructed in cell culture, between the somata of two functionally well-characterized neurons, right pedal dorsal 1 (RPeD1, the giant dopaminergic neuron) and visceral dorsal 4 (VD4). Clinically relevant concentrations of sevoflurane (1-4%) were tested for their effects on synaptic transmission and the intrinsic membrane properties of soma-soma paired cells. RPeD1- induced inhibitory postsynaptic potentials (IPSPs) in VD4 were completely and reversibly blocked by sevoflurane (4%). Sevoflurane also suppressed action potentials in both RPeD1 and VD4 cells. To determine whether the anesthetic-induced synaptic depression involved postsynaptic transmitter receptors, dopamine was pressure applied to VD4, either in the presence or absence of sevoflurane. Dopamine (10(-]5) M) activated a voltage-insensitive K(+) current in VD4. The same K(+) current was also altered by sevoflurane; however, the effects of two compounds were nonadditive. Because transmitter release from RPeD1 requires Ca(2+) influx through voltage-gated Ca(2+) channels, we next tested whether the anesthetic-induced synaptic depression involved these channels. Individually isolated RPeD1 somata were whole cell voltage clamped, and Ca(2+) currents were analyzed in control and various anesthetic conditions. Clinically relevant concentrations of sevoflurane did not significantly affect voltage-activated Ca(2+) channels in RPeD1. Taken together, this study provides the first direct evidence that sevoflurane-induced synaptic depression involves both pre- and postsynaptic ion channels.
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PMID:Sevoflurane induced suppression of inhibitory synaptic transmission between soma-soma paired Lymnaea neurons. 1056 48

beta-beta'-iminodipropionitrile (IDPN)-induced monoamine and hydroxyl radical changes in the rat brains were studied. IDPN caused decreases in 5-HT and 5-HIAA levels in all brain regions, strongly indicating that IDPN's neurotoxicity primarily affects 5-HT containing neurons. Dopamine and its metabolites' levels decreased in the some regions, most likely due to depression of dopamine metabolic turnover. Our results more clearly demonstrate IDPN-induced monoamine alterations in the rat brain more than previous reports. To clarify one of the pathogenesis of IDPN-induced neurological disorders, we measured hydroxyl radical levels. 2,3-DHBA increased at 1st day, and decreased in some regions at 7th days after discontinuing IDPN. We conclude, hydroxyl radical formation causes neuronal damage, and monoamine changes contribute to IDPN-induced neurological disorder.
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PMID:IDPN-induced monoamine and hydroxyl radical changes in the rat brain. 1076 86

The pathogenesis of the alterations in motor response that complicate levodopa therapy of Parkinson's disease remains obscure. Several experimental and clinical observations strongly suggest that changes in striatal activity may be crucial for this physiopathological condition. Accordingly, it has been postulated that dyskinesia might be due to abnormal activity of the corticostriatal pathway. Here, we review the physiological and pharmacological mechanisms underlying glutamatergic regulation of striatal neurons by the corticostriatal projection. In particular, we discuss the role of both (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors in the control of the short- and long-term efficacy of corticostriatal transmission. Indeed, repetitive cortical activation can generate either long-term depression or long-term potentiation (LTP) at corticostriatal synapses depending on the subtype of glutamate receptor activated during the induction phase of these forms of synaptic plasticity. Dopamine plays an important function in the regulation of both forms of synaptic plasticity. Dopamine denervation abolishes the physiological corticostriatal plasticity by producing biochemical and morphological changes within the striatum. We have recently observed a 'pathological' form of LTP at the corticostriatal synapse during energy deprivation. We speculate that this 'pathological' LTP, depending on the activation of NMDA glutamate receptors located on spiny striatal neurons, might play a role in the generation of levodopa-induced dyskinesia.
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PMID:Levodopa-induced dyskinesia: a pathological form of striatal synaptic plasticity? 1076 33

Atropine has previously been found to suppress visually induced myopia both in animals and humans. The mechanism of its action is unclear. We have studied its retinal effects in an in vitro preparation, using the retina-pigment epithelium-choroid complex of the chick eye. In vivo, deprivation myopia was induced by translucent goggles. Atropine solution was injected into the vitreous at two-day intervals. Dopamine release from the retina following atropine injection in vivo and from the in vitro retina preparation was quantified by HPLC-EC. In vitro preparations of the isolated chick retina-pigment epithelium-choroid were superfused with atropine. Light-induced potentials (local ERG), slow standing potentials from the retinal pigment epithelium/neural retina, and extracellular potassium concentrations were recorded. In line with previous findings, intravitreal injections of atropine (25 microg, 250 microg) reduced deprivation myopia in a dose-dependent manner. Atropine increased the release of the neurotransmitter dopamine into the superfusate in vitro at 100-500 microM and into the vitreous in vivo at 250 microg. Before an increase was measured in the vitreous, the retinal dopamine content was elevated. In concentrations equivalent to the intravitreal concentration to suppress myopia in vivo (200-800 microM), atropine induced spreading depression (SD) in the in vitro preparation. In contrast, muscarinic agonists, acetylcholine and pilocarpine, did not induce SD. Atropine reduced the ERG b- and d-wave, led to damped oscillations of RPE potentials, and reversed the ERG c-wave. Atropine suppressed myopia only at doses at which severe nonspecific side effects were observed in the retina. Atropine seems to intrude massively into the vital functions of the retina as indicated by the occurrence of SD. We conclude that atropine, by inducing SD, boosts neurotransmitter release from cellular stores, which may cancel out a presumed retinal signal that controls eye growth and through this, myopia.
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PMID:Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick. 1082 71


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