Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.
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PMID:Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission. 135 99

A single administration of the psychostimulant sydnocarb activates tyrosine hydroxylase (TH) in synaptosomes of rat brain hypothalamus and striatum. The inhibitory effect of dopamine (DA) in synaptosomes of the striatum is potentiated. A single administration of amphetamine activates the response in synaptosomes of the hypothalamus and activates it in the striatum. Amphetamine does not exert any effect on the inhibitory effect of DA. Chronic administration of sydnocarb activates synaptosomal TH in the hypothalamus and inhibits it in the striatum. Fifteen minutes after the last injection of the two-week sydnocarb treatment the regulatory effect of DA in respect to tyrosine hydroxylation is considerably reduced. Thirty minutes after the concluding injection of the 2-week amphetamine treatment TH is found to be activated in the hypothalamus and inhibited in the striatum. Twenty-four hours after the treatment is completed the reverse relations are observed. The regulatory inhibitory effect of DA in respect to TH was significantly reduced in both versions of experiment.
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PMID:[Comparative effect of the psychostimulants sidnocarb and fenamin on the tyrosine hydroxylase activity of the brain synaptosomes in rats]. 286 9

Rats subjected to a unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine pathway were given transplants of cultured fetal human sympathetic neurons. Amphetamine-induced turning behavior in these rats was reversed by the transplants after 1.5-4.5 months. The presence of transplanted neurons and their processes was demonstrated by immunohistochemistry for tyrosine hydroxylase.
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PMID:Functional recovery in a rat model of Parkinson's disease following transplantation of cultured human sympathetic neurons. 287 5

Adult young rats were subjected to a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway and then given intrastriatal grafts of human fetal adrenal chromaffin cell cultures. Amphetamine-induced ipsiversive turning behavior in the lesioned rats was largely reversed in four of eight rats given such transplants when tested at 1.5 and 4.5 months post-transplantation. Two rats showed a transient recovery at 1.5 months followed by deterioration at 4.5 months, while two other rats showed continuous deterioration. Six rats given sciatic nerve grafts as controls all showed deterioration from the pretransplantation levels. Catecholamine fluorescent and immunohistochemical examination of chromaffin-cell-transplanted brains demonstrated neurons and neuronal processes positive for catecholamines or tyrosine hydroxylase in the transplanted area. This transplantation of cultured human fetal cells to an animal model may provide the necessary basic experimental system for assessing the possible utility of human neuronal transplants.
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PMID:Transplantation of cultured human adrenal chromaffin cells into 6-hydroxydopamine-lesioned rat brain. 290 89

1. Intracisternally administered metaraminol, alpha-methyl-octopamine, alpha-methyl-m-tyramine, and alpha-methyl tyramine were found to lower brain noradrenaline without having an effect on brain dopamine.2. Amphetamine, mephentermine, and norephedrine had no effect on brain catecholamines after intracisternal injection.3. There was no reduction in brain dopamine content after intracisternal injection of alpha-methyl-m-tyramine, yet the resulting brain concentration of alpha-methyl-m-tyramine was several times higher than after intraperitoneal injection of alpha-methyl-m-tyrosine, which decreased brain dopamine.4. The decreased synthesis of labelled catecholamines from (14)C-tyrosine after alpha-methyl-m-tyrosine suggested that this compound inhibits tyrosine hydroxylase in addition to its action of displacing brain amines.
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PMID:Effects of amphetamine derivatives on brain dopamine and noradrenaline. 490 7

The motor activity of groups of three mice was increased by yohimbine at doses up to 3 mg/kg intraperitoneally. The turnover of dopamine and noradrenaline in the mouse brain, as assessed by the disappearance of catecholamines following treatment with the tyrosine hydroxylase inhibitor alpha-methyltyrosine, was accelerated by yohimbine with a peak effect after 10 mg/kg intraperitoneally. Prazosin (3 mg/kg i.p.) completely antagonized the stimulatory effect of yohimbine on motor activity and on dopamine turnover but it somewhat potentiated the stimulatory effect on the turnover of noradrenaline. Amphetamine reversed the prazosin-induced hypomotility, indicating that prazosin can selectively block postsynaptic alpha 1-receptors. Yohimbine did not stimulate motor activity following 10 mg/kg and it retarded the turnover of dopamine following 30 mg/kg. These actions might be due to blockade of postsynaptic alpha-receptors by yohimbine. The data indicate that yohimbine at low doses stimulates motor activity and dopamine turnover by selectively blocking alpha 2-autoreceptors leading to increased release of noradrenaline and subsequent activation of post-synaptic alpha 1-receptors.
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PMID:Selective blockade of brain alpha 2-autoreceptors by yohimbine: effects on motor activity and on turnover of noradrenaline and dopamine. 629 37

Rat brain striatal reduced biopterin (BH4) levels vary diurnally by 2-fold, oscillating around a concentration of 3 micrometer. D-Amphetamine consistently induced a decrease in BH4 levels that did not exceed 25 to 30% with increasing doses; recovery of control levels required several hours. A large number of other psychotropic drugs, including other stimulants and phenylethylamine congeners, failed to induce a similar change. The amphetamine effect was blocked by methylphenidate and reserpine. The prolonged time for BH4 recovery could be explained by an amphetamine-induced functional uncoupling of quinonoid dihydropteridine reductase from striatal tyrosine hydroxylase as reported for various cofactor analogs, leading to spontaneous isomerization of the partially reduced pterin to its nonquinonoid form, which is not a substrate for the BH4 regenerating enzyme. If relevant to dopamine biosynthesis, such an uncoupling phenomenon might account for a unique neuropharmacology of the postamphetamine state.
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PMID:The influence of D-amphetamine on rat brain striatal reduced biopterin concentration. 719 28

Reconstruction of the nigrostriatal pathway by long axon growth derived from dopamine-rich ventral mesencephalic (VM) transplants grafted into the substantia nigra may enhance their functional integration as compared to VM grafts implanted ectopically into the striatum. Here we report on a novel approach by which fetal VM grafts are implanted unilaterally into the substantia nigra (SN) of 6-hydroxydopamine (6-OHDA)-lesioned neonatal pups at postnatal day 3 (P3) using a microtransplantation technique. The results demonstrate that homotopically placed dopaminergic neurons survive and integrate well into the previously 6-OHDA-lesioned neonatal SN region. Moreover, the tyrosine hydroxylase (TH)-positive neurons extended axons rostrally along the white matter tract of the internal capsule closely following the course of the original nigrostriatal pathway. The graft reestablished a TH-positive axon terminal network in the ipsilateral caudate-putamen, with the highest density in the medial and central parts. Retrograde labeling with Fluoro-Gold from the host striatum demonstrated that most of the transplant neurons giving rise to the graft-derived fiber outgrowth were TH-positive, but revealed also a small proportion of projecting neurons which were TH-negative. Amphetamine-induced striatal Fos expression was normalized in the caudate-putamen ipsilateral to the intranigral VM grafts, showing hyperexpression in some areas of the striatum, and the apomorphine-induced Fos expression seen in the 6-OHDA-lesioned animals was completely reversed on the grafted side. These findings indicate that the graft-derived dopaminergic reinnervation of the striatum is functional. The microtransplantation strategy may provide new avenues for the exploration of morphological and functional integration of fetal dopamine neurons in the nigrostriatal system and give new insights into the mechanisms controlling long-distance axon growth in the brain.
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PMID:Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway. 753 63

A single administration of D-amphetamine and iprindole has been reported to produce selective, long-lasting decreases in brain dopamine (DA) content because of axon terminal degeneration. It has been found that the noncompetitive glutamate (GLU) antagonist, MK 801, blocks D-amphetamine-induced DA depletion in iprindole-treated rats. In the present study, the effect of D-amphetamine (9.2 mg/kg) and iprindole (10 mg/kg) on the extracellular concentrations of DA and GLU was determined in the striatum of awake, freely moving rats by the use of in vivo microdialysis. D-Amphetamine significantly increased DA and GLU efflux in the striatum of iprindole-treated rats as compared to the vehicle-treated group. The increase in the extracellular concentration of GLU occurred 4-6 hr following drug administration. The concentration of DA was decreased significantly in the striatum of D-amphetamine and iprindole-treated rats 7 days following administration as compared to the vehicle-treated group. Inhibition of tyrosine hydroxylase after alpha-methylparatyrosine (150 mg/kg) administration attenuated D-amphetamine-induced DA and GLU release. The DA antagonist, haloperidol (1 mg/kg), blocked D-amphetamine-induced GLU release without affecting the increase in the extracellular concentration of DA produced by the combination of D-amphetamine and iprindole. Both alpha-methylparatyrosine and haloperidol blocked the depletion of DA in the striatum 7 days after D-amphetamine and iprindole as compared to the vehicle group. In addition, administration of MK-801 (2 mg/kg) 2 hr after D-amphetamine significantly attenuated the long-term (7 day) decrease in striatal DA content produced by the combination of D-amphetamine and iprindole.2+
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PMID:Effect of D-amphetamine on the extracellular concentrations of glutamate and dopamine in iprindole-treated rats. 790 85

When embryonic ventral mesencephalic tissue containing nigral dopamine (DA) neurons is transplanted into adult DA-depleted striatum, synaptic connections form and behavioral effects are observed. This study investigated the cotransplantation of embryonic striatal tissue as a means of enhancing the innervation, survival, and functional effects of nigral transplants. Rats neonatally DA-depleted, via bilateral intraventricular injections of 6-hydroxydopamine, developed turning in response to amphetamine and stress following unilateral transplantation of either nigral or combination nigral-striatal cell suspensions. Animals with cotransplants developed higher levels of turning to both stimuli and maintained these responses for a longer period of time post-transplantation, when compared with animals receiving transplants of nigral cells alone. In addition, these combination transplants required fewer dopaminergic cells to produce a strong behavioral effect on the host. Dense patches of tyrosine hydroxylase (TH)-immunoreactive fibers were observed within the cotransplants, yet no greater outgrowth of DA fibers into host striatum was detected. Amphetamine produced widespread induction of the immediate-early gene c-fos in cells of host striatum that extended beyond the transplant-derived DA innervation. After both amphetamine and stress, Fos protein was found within both types of transplants, but these Fos-immunoreactive cells did not colocalize with TH-immunoreactive cells nor dense TH-immunoreactive patches within the grafts. Thus, cotransplanted embryonic striatal tissue augments the effects of ventral mesencephalic transplants, possibly by providing a trophic influence that enhances the function of the DA cells without increasing cell survival.
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PMID:Enhanced efficacy of nigral-striatal cotransplants in bilaterally dopamine-depleted rats: an anatomical and behavioral analysis. 791 45


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