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)

Food intake, plasma and brain amino acid concentrations, liver amino acid catabolic enzyme activities, and whole-brain neurotransmitter and metabolite concentrations were measured in young rats adapted for 11 d to diets containing from 5 to 75% (in increments of 5%) casein. Food intake was depressed initially in rats fed diets containing 5, 10% or greater than 35% casein. For the duration of the experiment, food intakes of the groups fed the higher protein diets improved on successive days; the length and severity of the depression were proportional to the protein content of the diet fed. Rats fed low levels of protein grew poorly, and their food intake remained depressed. The gradual improvement in growth and food intake of rats fed diets containing more than 35% casein was accompanied by dramatic increases in the activities of serine-threonine dehydratase (SDH, EC 4.2.1.16) and glutamate-pyruvate aminotransferase (GPT, EC 2.6.1.1) in liver. The increase in amino acid catabolic activity was accompanied by decreases in the concentrations of most amino acids in plasma and brain. However, concentrations of branched-chain amino acids, in both plasma and brain, increased in direct proportion to the protein concentration of the diet fed. As a result of these reciprocal responses, the total concentration of indispensable amino acids in brain (IAA) was maintained within a narrow range of values, despite a sixfold range of protein intakes. Whole-brain concentrations of norepinephrine, dopamine and serotonin were not correlated with dietary protein concentration, total food intake or protein intake. Brain concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were correlated inversely with protein intake and that of 3,4-dihydroxyphenylacetic acid was correlated directly with food intake. Protein intake appeared to be related to the animal's ability to maintain brain total IAA content between some upper and lower limits. Our results indicate that this was accomplished initially through downward adjustment of protein intake and subsequently through an increase in catabolic capacity for the amino acids.
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PMID:Adaptation of rats to diets containing different levels of protein: effects on food intake, plasma and brain amino acid concentrations and brain neurotransmitter metabolism. 285 80

The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
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PMID:The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. 287 93

Concentrations of the amines and amine metabolites dopamine (DA), noradrenaline (NA), adrenaline (A), serotonin (5-HT), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and of the peptides, vasopressin (AVP), vasoactive intestinal polypeptide (VIP), thyrotropin releasing hormone (TRH) and cholecystokinin (CCK) were measured in lumbar cerebrospinal fluid (CSF) in patients with depression and compared with that of controls. Diagnostic classifications were performed according to ICD-9 and the Newcastle Rating Scales for Depression. The severity of depression was measured by Bech-Rafaelsen melancholia scale. Significantly decreased concentrations of CSF-A and AVP were found in as well endogenous as in non-endogenous depression, whereas reduced levels of CSF-VIP were found only in the non-endogenous group. CSF-5-HT and DA were significantly increased in endogenously depressed patients. In these studies patients with non-endogenous depression were not included. No relationship between severity of depression and concentrations of neurotransmitters was found. For most of the neurotransmitters no correlation between concentrations measured at the lumbar and at the ventricular level seems to exist. This finding indicates that measurements on CSF collected from the lumbar sack not necessarily are indicative for concentrations measured at more central levels. Although several transmitter systems most likely are disturbed in depression, results from studies on lumbar CSF should be interpreted with precaution, until further information about origin and distribution of neurotransmitters in CSF has been obtained.
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PMID:Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? 290 16

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.
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PMID:Therapeutic effects of serotonin uptake inhibitors in depression. 293 76

The potential role of autoreceptors in regulating the activity of serotonin-containing dorsal raphe (RD) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro in the mouse. RD neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat RD cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. The inhibitory effect of tryptophan and chlorimipramine was abolished by pretreatment with p-chlorophenylalanine, while that of LSD was not. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in RD neuron activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total suppression of raphe cell activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of RD neuron activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cyproheptadine and methysergide produced no significant change in RD cell activity. The 5HT reuptake blocker, fluoxetine, produced a total suppression of RD neuron activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Do serotonin-containing dorsal raphe neurons possess autoreceptors? 294 13

Focal cortical freezing lesions in rats caused a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity (Pappius, 1981). Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere (Pappius and Dadoun, 1987). In contrast, norepinephrine (NE) was decreased bilaterally, while levels of dopamine and its metabolites were not affected (Pappius and Dadoun, 1986). To determine if the changes in these neurotransmitters are of functional importance and mediate the observed changes in LCGU, the effects of inhibition of 5-HT synthesis with p-chlorophenylalanine (PCPA) and alpha 1-adrenergic blockage with prazosin (PZ) on cerebral metabolism and biogenic amine content in injured brain were studied. At doses of PCPA ineffective on LCGU (50 and 100 mg/kg) brain trauma still resulted in increased 5-HT metabolism. PCPA at doses which selectively ameliorated the depression of cortical LCGU in the lesioned hemisphere (200 and 300 mg/kg) completely prevented changes in 5-HT and 5-hydroxyindoleacetic acid seen following traumatization in untreated animals. These results provide evidence that decreased LCGU in lesioned brain is due to an activation of the serotonergic system. Prazosin (1 mg/kg) given 30 min before the lesion significantly increased cortical glucose utilization in the injured hemisphere and was even more effective when the treatment was continued for 3 days. Prazosin did not modify changes in cortical biogenic amines seen in untreated animals. The data are in agreement with a postulated inhibitory role of serotonin and norepinephrine in the cerebral cortex and implicate both neurotransmitters in functional alterations associated with injury.
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PMID:Significance of biogenic amines in functional disturbances resulting from brain injury. 297 13

Specific binding of [3H]imipramine to its recognition sites in frontal cortex and levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) as well as uptake of serotonin by crude synaptosomal (P2) fraction were determined in a group of rats chronically (for 21 days) treated with different types of antidepressant drugs: nortriptyline, fluoxetine, iprindole, phenelzine (10 mg/kg per day), maprotiline (20 mg/kg per day) and vehicle only (controls). Quantitative analysis of imipramine competition curves confirmed the existence of two classes of [3H]imipramine sites: high-affinity with IC50 and 11.2 nM and low-affinity with IC50 of 630 nM for the competing ligand. The proportion of high- and low-affinity sites was 73 +/- 4 and 26 +/- 4%, respectively. Chronic treatment with all antidepressant drugs except iprindole significantly decreased the affinity but not the proportion of high-affinity sites for imipramine. IC50 of imipramine at low-affinity sites was even more markedly increased at low-affinity sites by all treatments except for phenelzine. Fluoxetine was by far the most effective in altering the affinity of both high- and low-affinity [3H]imipramine recognition sites. Both NE and 5-HT levels were significantly enhanced only by phenelzine treatment, whereas 5-HT and 5-HIAA levels were found to be lower after fluoxetine. Kinetics of 5-HT uptake were altered significantly only in rats treated with fluoxetine: rate of 5-HT uptake (Vmax) was decreased by 43% and Km value increased from 104 to 184 nM. Changes in affinity of imipramine for its binding sites were not found to be associated with the effect of tested drugs on 5-HT levels or uptake. They may be due to adaptive alterations in physico-chemical properties of binding proteins although the presence of residual drug interfering with the binding assay cannot be excluded. The observed changes are likely to represent the condition during chronic administration of these drugs in clinical therapy of depression.
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PMID:Regulation of high- and low-affinity [3H]imipramine recognition sites in rat brain by chronic treatment with antidepressants. 304 Apr 30

Interactions of lead and niacin were studied in growing broiler chicks fed one of four experimental diets from day-old to 3 wk of age. The diets were a low niacin basal diet (LN), the basal diet supplemented with 40 mg of niacin/kg (control), the basal diet supplemented with 2000 mg lead/kg, as lead acetate (LN + Pb) and the basal diet supplemented with both niacin and lead (control + Pb). Growth and feed efficiency were reduced significantly by lead. The lead-associated growth depression was less severe in chicks fed the low niacin diet as indicated by a significant lead X niacin interaction. The relative weights of two brain regions (telencephalon and diencephalon) and the adrenal glands were greater in lead-treated chicks than in their nonlead-treated counterparts. Plasma and telencephalon tryptophan were lower in lead-treated chicks than in nonlead-treated chicks. Diencephalon tryptophan was lower in chicks fed the LN diet than in chicks fed the control diet. Brain serotonin was lower and 5-hydroxyindoleacetic acid was higher in both brain regions of lead-treated chicks than in nonlead-treated chicks. The data indicate that tryptophan and serotonin metabolism were altered by lead treatment, whereas niacin was without effect. The interaction of lead and niacin on growth does not appear to be related to alterations of serotonin metabolism in the central nervous system.
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PMID:Effect of lead and niacin on growth and serotonin metabolism in chicks. 333 32

Eighteen unmedicated patients suffering from major depressive disorder with melancholia (DSM-III) were examined for abnormalities in peripheral serotonin (5-HT) and related metabolites. Serotonin in platelet-free plasma and in platelets from melancholics was significantly reduced to 30% and 60% of their respective control values. Plasma 5-hydroxyindoleacetic acid was also found to be reduced, but not significantly. Other plasma compounds related to 5-HT (indoleacetic acid, total tryptophan, and free tryptophan) were found to be unchanged in these patients. Of all variables, only platelet 5-HT was affected while patients were on clomipramine (CIM) treatment. After 2 weeks on CIM (100-150 mg/day, orally), platelet 5-HT was reduced to 8% of pretreatment values, but plasma 5-HT did not change and continued to be reduced upon clinical recovery. The existence of a distinct pool of plasma 5-HT that is clearly independent of the platelet pool is indicated by the differences observed in plasma and platelet 5-HT during CIM treatment, as well as by previous data from this laboratory. The very marked decrease in plasma 5-HT levels may be in accord with the central nervous system changes reported in depression and suggests the possibility of using plasma 5-HT as a peripheral indicator of abnormal serotonin function in melancholia.
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PMID:Decreased plasma serotonin in melancholic patients: a study with clomipramine. 367 70

The present study was undertaken in order to further explore the relationship between monoamine levels and hypothalamic-pituitary-adrenocortical (HYPAC) functioning and suicidal behavior in depressed patients. One hundred and thirty-two depressed inpatients participated in the NIMH Collaborative Study on the Psychobiology of Depression. Similar to previous reports, our suicide attempters were younger, more likely to be bipolar, had an earlier age at onset, and displayed more psychotic features. No correlation between cortisol hypersecretion or Dexamethasone Suppression Test (DST) nonsuppression and suicide attempts were found. Only the pre-DST evening plasma cortisol distinguished the groups, being lower in the attempter group. We were unable to confirm the previously reported correlation between cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and suicide attempts. Of the monoamines examined, only urinary and plasma 3-methoxy-4-hydroxphenylglycol (MHPG) differed between suicide attempters and nonattempters, showing lower levels in the attempter group. There was a trend for CSF MHPG in the same direction. This latter reduction was restricted to the bipolar group.
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PMID:Biochemistry and suicidal behavior in depressed patients. 373 Apr 60


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