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1.
(+/-)-3,4-Methylenedioxyamphetamine (MDA), an amphetamine analog with hallucinogenic activity, produced selective long-lasting reductions in the level of serotonin, the number of serotonin uptake sites, and the concentration of 5-hydroxyindoleacetic acid in rat brain. Morphological studies suggested that these neurochemical deficits were due to serotonin nerve terminal degeneration. These results show that MDA has toxic activity for serotonin neurons in rats and raise the question of whether exposure to MDA and related hallucinogenic amphetamines can produce serotonin neurotoxicity in the human brain. 相似文献
2.
Large doses of L-dopa given to mice produced marked increases in brain dopamine, no change in norepinephrine, and a remarkable decrease in brain serotonin. This reduction apparently results from a release or displacement, or both, of serotonin from its storage sites. 相似文献
3.
L-Dopa-induced release of cerebral monoamines 总被引：10，自引：0，他引：10
L-Dopa markedly increased the efflux of tritiated dopamine and tritiated serotonin from rat brain slices. This action appeared contingent on the decarboxylation of L-dopa to dopamine, since it could be blocked by an inhibitor of L-amino acid decarboxylase. Selective destruction of catecholamine-containing nerve terminals by 6-hydroxydopamine significantly decreased the uptake and release of tritiated dopamine but not that of tritiated serotonin. These observations support the hypothesis that a portion of exogenously administered L-dopa may enter central serotonin terminals and undergo decarboxylation to the amine with resultant displacement of the endogenous indoleamine from vesicular stores. 相似文献
4.
Narcolepsy: biogenic amine deficits in an animal model 总被引：1，自引：0，他引：1
I N Mefford T L Baker R Boehme A S Foutz R D Ciaranello J D Barchas W C Dement 《Science (New York, N.Y.)》1983,220(4597):629-632
Concentrations of biogenic amine metabolites in discrete brain areas differed significantly between dogs with genetically transmitted narcolepsy and age- and breed-matched controls. Dopamine and 3,4-dihydroxyphenylacetic acid were consistently elevated in the brains of narcoleptic animals, while homovanillic acid was not. Narcoleptic animals consistently exhibited lower utilization of dopamine and higher intraneuronal degradation of dopamine but no uniform decrease in serotonin utilization. Hence neuropathology appears to be associated with genetically transmitted canine narcolepsy. The data indicate a nonglobal depression of dopamine utilization or turnover or both. 相似文献
5.
Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice 总被引：35，自引：0，他引：35
1-Methyl-4-phenyl-1,2,5,6- tetrahydropyri dine ( MPTP ) is known to cause an irreversible destruction of the dopaminergic nigrostriatal pathway and symptoms of parkinsonism in humans and in monkeys. However, MPTP has been reported to act only minimally or not at all in several other animal species. When MPTP (30 milligrams per kilogram of body weight) was administered parenterally to mice, a decrease in concentrations of neostriatal dopamine and its metabolites, a decrease in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, and a disappearance of nerve cells in the zona compacta of the substantia nigra were observed. In contrast, MPTP administration had no effect on neostriatal concentrations of serotonin and its metabolites. MPTP administration thus results in biochemical and histological changes in mice similar to those reported in humans and monkeys and similar to those seen in Parkinson's disease in humans. The mouse should prove to be a useful small animal with which to study the mode of action of MPTP . 相似文献
6.
Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine 总被引：2，自引：0，他引：2
Hydrogen peroxide, dialuric acid, or 6-hydroxydopamine inhibited the uptake of dopamine, norepinephrine, and serotonin into rat brain synaptosomal preparations. The addition of catalase protected all systems, but catalase was only partially protective for 6-hydroxydopamine acting upon catecholamine uptake. The data show that 6-hydroxydopamine generates hydrogen peroxide and that hydrogen peroxide can damage the biogenic amine uptake systems. Part of the damage caused by the 6-hydroxydopamine that accumulates in the catecholamine nerve terminals in vivo may be attributed to the hydrogen peroxide. 相似文献
7.
Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders. 相似文献
8.
When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain. 相似文献
9.
Cloning of a serotonin transporter affected by antidepressants 总被引：35，自引：0，他引：35
A complementary DNA clone for a serotonin (5HT) transporter has been isolated from rat basophilic leukemia cells. The complementary DNA sequence predicts a 653-amino acid protein with 12 to 13 putative transmembrane domains. The 5HT transporter has significant homology to the gamma-aminobutyric acid, dopamine, and norepinephrine transporters. Uptake by CV-1 cells expressing the transporter complementary DNA resembles 5HT uptake by platelets and brain synaptosomes; it is sensitive to antidepressants, amphetamine derivatives, and cocaine. 相似文献
10.
Brain dopamine and serotonin receptor sites revealed by digital subtraction autoradiography 总被引：5，自引：0，他引：5
Autoradiography combined with image analysis permitted quantitative visualization of dopamine (D2) and serotonin (S2) binding sites in rat brain. Forebrain sections were incubated with tritiated spiroperidol alone or with tritiated spiroperidol plus unlabeled compounds that saturated the D2 or S2 sites. By subtracting the digitized image of an autoradiograph derived from the latter sections from that of the former, the D2 or S2 sites were specifically revealed. The resulting quantitative images demonstrate the differing anatomical distributions of these sites. The D2 site is largely restricted to the striatal complex (caudate-putamen, nucleus accumbens septi, and olfactory tubercle), whereas the S2 site is enriched in layer 5 of motor cortex, the perirhinal and cingulate cortices, and the claustrum. 相似文献
11.
Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin. 相似文献
12.
Schizophrenia is a debilitating mental illness that affects 1% of the population. Despite intensive study, its molecular etiology remains enigmatic. Like many common diseases, schizophrenia is multifactorial in origin, with both genetic and environmental contributions likely playing an important role in the manifestation of symptoms. Recent advances based on pharmacological studies, brain imaging analyses, and genetic research are now converging on tantalizing leads that point to a central role for several neurotransmitters, including dopamine, glutamate, and serotonin, that may interface with neurodevelopmental defects reflecting disease-related genetic aberrations. Here, we provide a brief overview of the parallel approaches being used to identify the molecular causes of schizophrenia and discuss possible directions for future research. 相似文献
13.
Reserpine, when administered to animals stressed by exposure to cold, does not induce sedation or appreciably lower brain serotonin, but markedly lowers brain norepinephrine. Reserpine in cold-exposed hypophysectomized rats elicits sedation and releases both amines equally. The results support the view that the tranquilizing action of reserpine is not related to brain norepinephrine loss but rather to change in the level of brain serotonin. 相似文献
14.
Zhang X Beaulieu JM Sotnikova TD Gainetdinov RR Caron MG 《Science (New York, N.Y.)》2004,305(5681):217
Dysregulation of brain serotonin contributes to many psychiatric disorders. Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in the brain. We report a functional (C1473G) single-nucleotide polymorphism in mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to decreased serotonin levels in PC12 cells. Moreover, in BALB/cJ and DBA/2 mice that are homozygous for the 1473G allele, brain serotonin tissue content and synthesis are reduced in comparison to C57Bl/6 and 129X1/SvJ mice that are homozygous for the 1473C allele. Our data provide direct evidence for a fundamental role of Tph2 in brain serotonin synthesis. 相似文献
15.
Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen level-dependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events. 相似文献
16.
The drug, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), depletes striatal dopamine levels in primates and certain rodents, including mice, and produces parkinsonian-like symptoms in humans and nonhuman primates. To investigate the consequences of grafting adrenal medullary tissue into the brain of a rodent model of Parkinson's disease, a piece of adult mouse adrenal medulla was grafted unilaterally into mouse striatum 1 week after MPTP treatment. This MPTP treatment resulted in the virtual disappearance of tyrosine hydroxylase-immunoreactive fibers and severely depleted striatal dopamine levels. At 2, 4, and 6 weeks after grafting, dense tyrosine hydroxylase-immunoreactive fibers were observed in the grafted striatum, while only sparse fibers were seen in the contralateral striatum. In all cases, tyrosine hydroxylase-immunoreactive fibers appeared to be from the host rather than from the grafts, which survived poorly. These observations suggest that, in mice, adrenal medullary grafts exert a neurotrophic action in the host brain to enhance recovery of dopaminergic neurons. This effect may be relevant to the symptomatic recovery in Parkinson's disease patients who have received adrenal medullary grafts. 相似文献
17.
By administering C(14)-la-beled tyrosine or H(3)-labeled 3,4-dihy-droxyphenylalanine to guinea pigs it has been possible to achieve sufficient labeling of the norepinephrine and dopamine in the brain to permit measurement of their turnover rates. The half-life of brain dopamine was about 2.5 hours. The half-life of norepinephrine was about 4 hours, suggesting a rate of synthesis of at least 0.03 to 0.04, microg/g per hr or 2.4 microg/day for the whole guinea pig brain. 相似文献
18.
Amphetamine: differentiation by d and l isomers of behavior involving brain norepinephrine or dopamine 总被引：4，自引：0，他引：4
d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is 1-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum. In behavioral studies, d-amphetamine is ten times as potent as 1-amphetamine in enhancing locomotor activity, while it is only twice as potent in eliciting a compulsive gnawing syndrome. This suggests that the locomotor stimulation induced by amphetamine involves central norepinephrine, while dopamine neurons play an important role in the induced compulsive gnawing behavior. Assessment of differential actions of d- and 1-amphetamine may be an efficient method to differentiate behaviors involving norepinephrine or dopamine in the brain. 相似文献
19.
Primary cultures of astrocytes from neonatal rat brain were incubated with tritiated serotonin. After fixation they were stained by immunofluorescence for the astrocyte-specific marker glial fibrillary acidic protein and processed for autoradiography. Silver grain density was increased over cells positive for glial fibrillary acidic protein and was reduced to background levels when sodium was omitted from the medium or the specific inhibitors of serotonin uptake fluoxetine and chlorimipramine were present. The results indicate that mammalian astrocytes can take up serotonin by a sodium-dependent, high-affinity system previously thought to be the exclusive property of serotonergic nerve endings. 相似文献
20.
Imaging dopamine receptors in the human brain by positron tomography 总被引：14，自引：0，他引：14
H N Wagner H D Burns R F Dannals D F Wong B Langstrom T Duelfer J J Frost H T Ravert J M Links S B Rosenbloom S E Lukas A V Kramer M J Kuhar 《Science (New York, N.Y.)》1983,221(4617):1264-1266
Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans. 相似文献