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  • 1
    Electronic Resource
    Electronic Resource
    Influence of Fluoxetine on Regional Serotonin Synthesis in the Rat Brain (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 67 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The aim of the present study was to test the hypothesis that there should be a difference between the effects of an acute and an 8-day (chronic) administration of fluoxetine (10 mg/kg) on the rate of serotonin [5-hydroxytryptamine (5-HT)] synthesis. The 5-HT synthesis rate was measured in discrete regions of the rat brain using the α-[14C]methyl-l-tryptophan autoradiographic method. The results show that the acute and chronic fluoxetine treatments influence the 5-HT synthesis rate in different ways. A single dose of fluoxetine induced a significant increase in 5-HT synthesis in the visual, auditory, and parietal cortices, substantia nigra, hypothalamus, ventral thalamus, and dorsal hippocampus. In contrast, after a chronic treatment a decrease was observed in the substantia nigra, caudate, and nucleus accumbens, the auditory, parietal, sensorimotor, and frontal cortices, and ventral tegmental area. A significant decrease in the rate of 5-HT synthesis was observed in the dorsal raphe after both the single and chronic treatments. The results suggest that extracellular 5-HT has a delayed influence on the brain 5-HT synthesis rate in structures with serotonergic terminals. The findings from the acute study could be important for patients who have just started receiving fluoxetine treatment, as an increase in the 5-HT synthesis rate might occur in the acute phase of their treatment. In addition, the findings from the chronic treatment study might give us a better understanding of how the brain serotonergic system adapts during a prolonged exposure to extracellular 5-HT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.67062434.x
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  • 2
    Electronic Resource
    Electronic Resource
    Determination of the Lumped Constant for the α-Methyltryptophan Method of Estimating the Rate of Serotonin Synthesis (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 64 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The lumped constant (LC) for the α-methyl-l-tryptophan method to convert the brain's uptake of labeled α-methyl-l-tryptophan into the regional rate of serotonin synthesis was estimated. The method involved independently estimating the unidirectional uptake constant of the tracer (α-[14C]methyl-l-tryptophan) to the tissue and the tracee (tryptophan) (with the addition of a radioactive compound) and calculating their ratio. The LC was estimated from logarithmically transformed data. Similar experiments were performed using rats treated with the drug probenecid, which blocks the efflux of 5-hydroxyindoleacetic acid (a metabolite of serotonin) from the brain. The experiments using probenecid, corrected for the difference in the levels of plasma free tryptophan (increased in probenecid-treated rats) relative to control experiments, gave an average LC for the rat brain of 0.46 ± 0.14 (mean ± SD). This value was not significantly different from the one obtained in controls (0.43 ± 0.13). In addition, the LC was also calculated using unidirectional uptake constants in the probenecid-treated rats for α-methyl-l-tryptophan and l-tryptophan. This LC value was 0.39 ± 0.10. There was no significant difference between these three LC values. Thus, an average ± SD LC of 0.42 ± 0.07 for 28 brain structures investigated in this study was obtained. Statistically the LC obtained in different structures had a variability that could be accounted for by errors in measurements alone. In other words, dispersion in the LC values could be fully accounted for by chance alone. Data confirmed that the LC value did not change when the rate of serotonin synthesis was increased by probenecid treatment. We also showed that the rate of 5-hydroxyindoleacetic acid accumulation in probenecid-treated rats was 58 pmol g−1 min−1 (rat brain), which is about twice as much as reported by others for a normal rat. This difference could also be accounted for by the increase in the plasma level of free tryptophan in probenecid-treated rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.64020624.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of Acute Fluoxetine Treatment on the Brain Serotonin Synthesis as Measured by the α-Methyl-l-Tryptophan Autoradiographic Method (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 65 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of treatment with acute fluoxetine, a serotonin reuptake inhibitor, on the rate of serotonin synthesis in the rat brain was studied through autoradiography following intravenous administration of α-methyl-l-[3H]tryptophan. The rate of serotonin synthesis in fluoxetine-treated rats was compared with the rate measured in sham-treated rats (saline injection). Results showed a significant increase in the rate of synthesis in the majority of cerebral structures examined. The greatest increase (given as a percentage of rates in control animals) in the rate of serotonin synthesis was observed in the substantia nigra compacta (344%), hippocampus-CA3 (337%), dorsal hippocampus (283%), and caudate-putamen (232%). Fluoxetine had a less significant effect on the rate of synthesis in the pineal body (44%). Data suggest that acute fluoxetine treatment (30 mg/kg, i.p.) enhances the rate of serotonin synthesis in all the structures of rat brain examined in this work.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.65010250.x
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  • 4
    Electronic Resource
    Electronic Resource
    Synthesis, receptor binding, and target-tissue uptake of carbon-11 labeled carbamate derivatives of estradiol and hexestrol (1984)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 27 (1984), S. 509-513 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00370a013
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of Acute and Chronic Administration of the Serotonin1A Agonist Buspirone on Serotonin Synthesis in the Rat Brain (1999)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 72 (1999), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of acute and chronic administration of buspirone, a serotonin 5-HT1A agonist, on the 5-HT synthesis rates in various rat brain structures were investigated using α-[14C]methyl-L-tryptophan (α-[14C]MTrp) and an autoradiographic method. In the acute treatment study, buspirone (10 mg/kg) was injected subcutaneously 30 min before α-[14C]MTrp administration (30 μCi over 2 min) into a femoral vein. In the chronic treatment study, buspirone was given in a sustained fashion (10 mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. Rats were killed 60 and 150 min after α-[14C]MTrp administration (two-time point method). A single dose of buspirone induced a significant decrease of 5-HT synthesis throughout the brain with the exception of the pineal body. However, the chronic treatment with buspirone did not induce significant differences in 5-HT synthesis in the brain. There was no significant difference in plasma free tryptophan concentration between any of the groups. The unaltered 5-HT synthesis rates in the chronic treatment study likely reflect a normalization of this parameter due to a desensitization of 5-HT1A autoreceptors on the cell body of 5-HT neurons, which has been previously shown to occur following long-term treatment with 5-HT1A agonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1999.0722022.x
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  • 6
    Electronic Resource
    Electronic Resource
    Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serotonin synthesis rates were evaluated using α-[14C]methyl-l-tryptophan (α-MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p 〈 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5-hydroxytryptamine (5-HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13–25%) and the thalamus (22–40%). The largest increase in 5-HT synthesis after OBX was observed in the sensory-motor cortex (67%). 5-HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5-HT synthesis in some projection areas by disproportionally increasing 5-HT synthesis rates in specific brain regions and making more 5-HT available for neurotransmission. This imbalance in 5-HT synthesis and the subsequent elevation of tissue 5-HT may be responsible for the creation of non-physiological circuitry which may, in part, be reflected in the symptoms resembling human depression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01702.x
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional serotonin synthesis in the rat brain: an autoradiographic study (2002)
    Oxford, UK : Blackwell Science, Ltd
    Journal of neurochemistry 80 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of acute and repeat administration of the serotonin (5-HT)1 agonists TFMPP [N-(3-trifluoromethyl)phenylpiperazine hydrochloride] and CGS12066B [7-trifluoromethyl-4- (4-methyl-1-piperazinyl)pyrrolo[1,2-a]-quinoxaline dimaleate] were evaluated on 5-HT synthesis rates using the α-[14C]methyl-l-tryptophan (α-MTrp) autoradiographic method. In the acute treatment study, TFMPP (10 mg/kg) and CGS12066B (5 mg/kg) were injected intraperitoneally 30 min before an α-MTrp injection. In an acute study TFMPP reduced overall brain 5-HT synthesis, in the dorsal and median raphe, and in almost all of their projection areas, with the exception of the parietal, sensory-motor, and frontal cortices, the accumbens nucleus, and the caudate. Acute CGS12066B treatment did not have overall significant effect, but the rates did decrease in the cell body areas of 5-HT neurons. In a 7-day treatment with TFMPP (10 mg/kg/day) or CGS12066B (5 mg/kg/day), the 5-HT synthesis rates (24 h after last dose) decrease, with both compounds, in almost all of the nerve terminal structures. TFMPP reduced the synthesis in the dorsal and median raphe, while CGS12066B reduced it only in the dorsal raphe. This data suggests that after a 7-day treatment with TFMPP and CGS12066B, the rate of 5-HT synthesis in the dorsal raphe is restored and is reduced in many projection areas. The observed effects in the 7-day treatment could also be related to actions through the postsynaptic 5-HT1B sites and/or other 5-HT receptors since this compounds have limited selectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0022-3042.2002.00757.x
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  • 8
    Electronic Resource
    Electronic Resource
    Study of the brain serotonergic system with labeled α-methyl-l-tryptophan (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: α-Methyl-l-tryptophan (α-MTrp) is an artificial amino acid and an analog of tryptophan (Trp), the precursor of the neurotransmitter serotonin (5-HT). In this article we have summarized available data, which suggest that the measurement of the unidirectional uptake of α-MTrp and its conversion to 5-HT synthesis rates is a valid approach for the determination of brain 5-HT synthesis rates. The main feature on which the model is based is the trapping of labeled α-MTrp in brain tissue. An overview of opposing opinions, which suggest that there is a need for a metabolic conversion of tracer, is also presented and discussed critically. As with all biological modeling there is likely to be room for improvements of the proposed biological model. In addition, there are a limited number of clearly defined circumstances in which the method is confounded by the metabolism of labeled α-MTrp via the kynurenine pathway. Nonetheless, a significant body of evidence suggests that labeled α-MTrp is a useful tracer to study brain 5-HT synthesis in most circumstances. Calculation of 5-HT synthesis rates depends on the plasma-free tryptophan concentration, which, according to the balance of arguments in the literature, is a more appropriate parameter than the total-plasma tryptophan. The method, as proposed by us, can be used in conjunction with autoradiographic measurements in laboratory animals, and with positron emission tomography in large animals and humans. We review studies in animals looking at the normal control of 5-HT synthesis and the way in which it is altered by drugs, as well as initial studies investigating healthy humans and patients with neuropsychiatric disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00536.x
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  • 9
    Electronic Resource
    Electronic Resource
    α-Methyl-l-tryptophan as a tracer to study brain serotonergic system (1995)
    Springer
    Neurochemical research 20 (1995), S. 1353-1360 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00992511
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  • 10
    Electronic Resource
    Electronic Resource
    Acute and Chronic D-Fenfluramine Treatments Have Different Effects on Serotonin Synthesis Rates in the Rat Brain: An Autoradiographic Study (1999)
    Springer
    Neurochemical research 24 (1999), S. 1611-1620 
    Details
    ISSN: 1573-6903
    Keywords: D-fenfluramine ; α-[14C]methyl-L-tryptophan ; autoradiography, serotonin synthesis rate ; tryptophan hydroxylase ; dorsal raphe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of acute and chronic treatments with D-fenfluramine on the regional rates of serotonin (5-hydroxy-tryptamine; 5-HT) synthesis were investigated using the α-[14C]methyl-L-tryptophan (α-[14C]MTrp) autoradiographic method. In the first series of experiments, acute D-fenfluramine treatment (5 mg/kg; i.p.) given 20 min before the tracer injection significantly (p 〈 0.05) decreased 5-HT synthesis in the dorsal raphe, and significantly (p 〈 0.05) increased the rates in the cerebral cortices and caudate nucleus, when compared to the rates in the control rats (saline treated). In a second series of experiments, following a 7-day treatment with D-fenfluramine (5 mg/kg/day; i.p.), a significant (p 〈 0.05) decrease of 5-HT synthesis, in the dorsal raphe was observed, and significant (p 〈 0.05) increases were observed in the hypothalamus, the dorsal thalamus, the medial and lateral geniculate body and some brain stem regions (locus ceruleus, inferior and superior colliculus). No significant changes were observed in the cerebral cortices.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1021120603457
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