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)

The role of spinal pathways in the regulation of adrenal medullary tyrosine hydroxylase and catecholamines was studied in adult rats subjected to spinal cord transection at the third thoracic level. In these animals the sympathoadrenal preganglionic neurons were isolated from their supraspinal afferents. This treatment led after three days to a progressive reduction of tyrosine hydroxylase activity and dopamine content (as compared to unoperated controls) until at least the 10th day. The results of the administration of dexamethasone or adrenocorticotropic hormone to spinalized rats suggest that in these animals glucocorticoid hypersecretion is not involved in the decline of adrenal tyrosine hydroxylase and that in fact adrenocorticotropic hormone supplementation can prevent it. A neurogenic origin for the depression of adrenomedullary function is favoured because unilateral splanchnicotomy (which by itself does not affect adrenal tyrosine hydroxylase), prior to cord section, prevented the diminution of tyrosine hydroxylase activity in the denervated gland. The decline of adrenal tyrosine hydroxylase and dopamine after spinal section may result from a decrease of modulatory impulses to the adrenal from decentralized sympathoadrenal preganglionic neurons in the isolated cord, following the loss of a descending facilitation of these neurons and/or the release of a segmental interneuronal inhibition of these neurons from a descending inhibitory influence. Such descending pathways may decussate partially below the low cervical level because rats with hemisection of the cord at C6-C7 exhibited no decline of adrenal tyrosine hydroxylase or of dopamine measured on either side seven days postoperatively.
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PMID:Differential effects of transection of the spinal cord and splanchnic nerve on adrenal tyrosine hydroxylase and catecholamines. 285 54

The results reported here indicate that treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused significant changes in the dopamine-synthesizing enzyme, tyrosine hydroxylase. The authors examined the effects of two doses of MPTP on the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in the striatum, and also the time-course of these effects. Rats received an intraperitoneal loading dose, followed by a 24-hr infusion of MPTP (total doses of 21 or 42 mg) from subcutaneously-implanted osmotic pumps. Seven days after treatment, the activity of tyrosine hydroxylase was decreased by MPTP (42 mg); however, the activity of tryptophan hydroxylase was not affected. In time-course experiments, the activity of tyrosine hydroxylase was maximally reduced at 3 and 7 days after treatment with MPTP (42 mg). The activity of tryptophan hydroxylase did not significantly change at any time-point. Concurrent administration of haloperidol (HALO; 2 mg/kg, 4 doses) with MPTP significantly enhanced the depression of the activity of tyrosine hydroxylase in the striatum caused by MPTP, while treatment with haloperidol alone had no such effect. Concentrations of dopamine in the striatum were maximally decreased to approx. 50% of control in animals treated with haloperidol and MPTP (42 mg), whereas treatment with MPTP alone decreased concentrations of dopamine to approx. 70% of control.
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PMID:Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase and tryptophan hydroxylase in rat. 287 13

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

Manic depression is a severe cyclic mental illness that can be unipolar or bipolar and has a lifetime risk of approximately 7 per 1,000 in most populations. Families with multiple cases of manic depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission. Psychoactive antidepressant and stimulant drugs that help to ameliorate depression and mania are thought to act by affecting catecholamine neurotransmitter systems such as adrenaline, noradrenaline and dopamine, amongst others. Mutations affecting the tyrosine hydroxylase (TH) gene, which encodes the rate-limiting enzyme for the synthesis of these three neurotransmitters, might therefore be responsible for causing the manic depressive phenotype. We have studied three Icelandic kindreds amongst whom it appears that a single autosomal dominant disease allele is segregating. In these families there were 44 cases amongst 73 individuals at risk. Genetic linkage studies were carried out using clones encoding tyrosine hydroxylase the variable portion of the Harvey-ras-1 (HRAS1) locus and the variable region of the insulin gene (INS). All three markers are closely linked on chromosome 11 and were used to observe the segregation of restriction fragment length polymorphisms (RFLPs) in the three affected kindreds. We found no evidence for linkage to these markers in any of the three families. In contrast, Gerhard et al. found linkage between manic depression and HRAS1 in a single large Amish kindred. We conclude that there is genetic heterogeneity of linkage in manic depression. Therefore mutations at different loci are responsible for the manic depressive phenotype in the Amish and in Iceland.
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PMID:Molecular genetic evidence for heterogeneity in manic depression. 288 Dec 10

As determined by autoradiographic techniques, multiple high doses of methamphetamine elicited a reduction in dopamine receptor population (both D1 and D2) in several areas of the rat central nervous system. D1 receptors were labeled with the D1-selective antagonist, [3H]SCH 23390, and D2 receptors were labeled with the D2-selective neuroleptic, [3H]sulpiride. Scatchard analysis, obtained from saturation data in caudate-putamen, indicated that the receptor alterations were due to a decrease in the number of receptors (Bmax) without an apparent change in affinity (Kd). A time course demonstrated that five doses of methamphetamine were required to elicit significant changes in receptors in most brain areas examined. The onset of the receptor alterations in various brain regions correlated with the development of methamphetamine-induced depression of striatal tyrosine hydroxylase activity. In most brain areas, the dopamine receptors returned to normal within 7 days following methamphetamine.
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PMID:Methamphetamine-induced reduction in D1 and D2 dopamine receptors as evidenced by autoradiography: comparison with tyrosine hydroxylase activity. 289 Oct 82

The role of the serotonin uptake carrier in the methamphetamine-induced depression of serotonin synthesis was examined. In vivo, coadministration of citalopram or chlorimipramine with methamphetamine blocked the irreversible depression of tryptophan hydroxylase activity observed in the neostriatum and cerebral cortex after repeated administration of high doses of methamphetamine. The methamphetamine-induced reduction of neostriatal serotonin and 5-hydroxyindoleacetic acid was also attenuated by the two uptake inhibitors. In contrast, neither drug antagonized the depression of neostriatal tyrosine hydroxylase activity observed after methamphetamine administration. Citalopram also blocked the reversible inhibition of tryptophan hydroxylase activity observed after the acute administration of methamphetamine. In vitro, citalopram significantly inhibited methamphetamine-induced [3H]serotonin release from neostriatal slices. The results demonstrate that inhibitors of the serotonin uptake carrier can antagonize both the in vivo and in vitro effects of methamphetamine on serotonergic neurons. Furthermore, the methamphetamine-induced depression of serotonin synthesis is dependent upon a functional serotonin uptake system.
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PMID:Role of the serotonin uptake carrier in the neurochemical response to methamphetamine: effects of citalopram and chlorimipramine. 385 54

Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.
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PMID:Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. 610 22

Acute administration of methamphetamine produced a dose-dependent depression of tryptophan hydroxylase (TPH) activity. The depression was observed in several serotonergic nerve terminal regions of the rat brain and spinal cord. Complete recovery of TPH activity following methamphetamine treatment occurred in all regions, but the time to recovery varied with the dose administered. In contrast to TPH, tyrosine hydroxylase (TH) was not affected by a single injection of methamphetamine. The data are discussed in the context of the effects of single versus repeated doses of methamphetamine on tryptophan and tyrosine hydroxylase.
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PMID:Methamphetamine-induced depression of tryptophan hydroxylase: recovery following acute treatment. 612 Aug 43

A study was made of the central effects of tuftsin (Thr-Lys-Pro-Arg) and its analogs (Leu1-tuftsin, D-Arg4-tuftsin) on the dopamine-dependent behavior and tyrosine hydroxylase (TH) activity. It was shown that the absence of direct effect of tuftsin and Leu1-tuftsin on postsynaptic dopaminergic receptors, revealed in experimental rotational behavior, correlates with a decrease in TH activity in the rat hypothalamus and striatum. Depression of the rotational behavior and increased activity of TH under the effect of D-Arg4-tuftsin suggest that this analog can modulate postsynaptic dopaminergic receptors by the antagonism type.
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PMID:[Analysis of the neurochemical mechanisms of the psychotropic action of tuftsin and its analogs]. 612 53

The effects of treatment with and withdrawal from lithium (Li, 2 mmol/kg) on central catecholamine systems in rat brain were investigated. Synthetic parameters were found to be unchanged after treatment, but abrupt withdrawal resulted in enhanced activity of tyrosine hydroxylase. Noradrenaline levels in most brain regions examined were depressed following both short- and long-term Li administration, with a further decrease in content in the pons but enhanced cortical levels on withdrawal. Li administration resulted in elevated 3,4-dihydroxyphenylacetic acid levels, whereas withdrawal caused an enhancement of homovanillic acid content and depression of 3-methoxy-4-hydroxyphenyl glycol levels. It appears that the changes in central catecholamine systems are qualitatively the same following both short- and long-term Li treatment, as are the consequences of abrupt Li withdrawal. It is suggested that Li administration results in a disruption of catecholamine storage processes, while withdrawal from Li does not result in a simple return towards normal states.
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PMID:Comparison of the changes in central catecholamine systems following short- and long-term lithium treatment and the consequences of lithium withdrawal. 615 62


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