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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
    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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  • 3
    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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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats (1995)
    Springer
    Journal of neuro-oncology 24 (1995), S. 229-240 
    Details
    ISSN: 1573-7373
    Keywords: cisplatin ; intracarotid chemotherapy ; multi-tracer autoradiography ; blood brain barrier ; cerebral blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to find the reliable parameter(s) for the detection of early neurotoxicity following intracarotid (IC) administration of cisplatin. IC administration was performed for 60 minutes in female Wistar rats derived into four groups according to the dose given (1 mg, 1.2 mg, and 1.5 mg of cisplatin, and normal saline in control rats). Blood-brain barrier (BBB) permeability and local cerebral blood flow (LCBF) were measured by a double-tracer autoradiography technique using 1-[14 C]-α-aminoisobutyric acid (14 C-AIB) and 4-[18 F] fluoroantipyrine (18 F-FAP), respectively. Blood chemistry and neuropathology were also examined. BBB permeability was incereased only on the ipsilateral side. This increase was dose-dependent, preceded the brain necrosis, and was statistically significant in the hypothalamus [1.2 mg group), auditory cortex and caudoputamen (1.5 mg group). Renal dysfunction was often observed. The changes in the LCBF did not occur until brain necrosis was noticeable. These findings demonstrate that the increase in the BBB permeability provides a sensitive and reliable indication of an early toxicity to brain tissue following IC administration of cisplatin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01052839
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  • 6
    Electronic Resource
    Electronic Resource
    Relationship Between Drug Delivery and the Intra-arterial Infusion Rate of SarCNU in C6 Rat Brain Tumor Model (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 235-246 
    Details
    ISSN: 1573-7373
    Keywords: brain tumor ; intra-arterial administration ; chemotherapy ; drug delivery ; drug streaming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influences of the flow rate on the concentration and distribution of drug in the rat brains and brain tumors after intra-arterial (intra-carotid) administration of [3H]SarCNU (sarcosinamide chloroethyl-1-nitrosourea) were examined. Results obtained at three flow rates via intra-carotid route were compared to those obtained with intravenous administrations. Adult female Wistar rats bearing C6 brain tumor were randomized into four-groups. Groups 1 (G.1) to 3 (G.3) received intra-arterial injection and Group 4 (G.4) received intravenous administration of [3H]SarCNU. G.1 (slow infusion rate) was administered 1 ml of [3H]SarCNU solution over 60 min (0.017 ml/min), Group 2 (G.2; medium infusion rate): 0.2 ml over 5 min (0.04 ml/min), G.3 (fast infusion rate): 1 ml over 5 min (0.2 ml/min), and G.4 (intravenous infusion): 1 ml intravenously over 5 min. Quantitative autoradiographic method was used to measure the concentration and the distribution of [3H]SarCNU in the brain and the brain tumors. The tissue uptake constant of SarCNU in both viable (tumor tissue excluding necrosis) and peak regions (the area of tumor containing top 20% of the tracer concentration) of the intra-arterial injection groups were significantly higher (p〈0.0001) than those in the intravenous group. The mean concentrations of the viable tumor in the intra-arterial groups were 2.92 (G.1), 16.06 (G.2), and 20.8 (G.3) times higher than those of intravenous group. Between the intra-arterial groups, the mean concentration in the viable tumors of G.1 (slow flow rate) was significantly (p〈0.0001) lower than in G.2 and G.3. However, there was no significant difference between G.2 and G.3. In three intra-arterial groups the mean concentration delivery ratios of the brain tumors were high and ranged from 3.07 (G.3) to 3.87 (G.2), but there was no significant difference between them. Only G.4, intravenous group, showed significantly (p〈0.005) lower concentration delivery ratio, 1.26. These results suggest that higher infusion rate in the intra-arterial chemotherapy could have an effect not only on the streaming phenomenon which results in the brain toxicities, but also on the increase in the concentration and the sufficient distribution of a drug in tumors. By finding chemotherapeutic agents to which tumors show high sensitivity and using intra-arterial administration of these agents at more effective flow rate, better clinical results could be achieved in the treatment of patients with malignant brain tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006104220315
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  • 7
    Electronic Resource
    Electronic Resource
    Assessment of the peripheral benzodiazepine receptors in human gliomas by two methods (1998)
    Springer
    Journal of neuro-oncology 38 (1998), S. 19-26 
    Details
    ISSN: 1573-7373
    Keywords: autoradiography ; tumor differentiation ; liquid scintillation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was designed to evaluate the density of peripheral benzodiazepine receptor (PBR) sites as a function of tumor malignancy in human gliomas, and to compare the results obtained with autoradiographic and liquid scintillation measurements performed on the same tissue specimens. In vitro binding of [3H]PK-11195[1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isog uinoline carboxamide] to human gliomas in radioligand binding studies revealed a significantly higher level (about 3 fold) of PBR binding sites in both low grade and high grade gliomas as compared to normal cortex. The Bmax (mean ± SD) of high and low grade gliomas, when entire tissue sections were measured by autoradiography, was 5.5 ± 0.3 pmol/mg-tissue (n = 5) and 1.8 ± 0.9 pmol/mg-tissue (n = 6), respectively, although it was evident that there was area of hot spots in the high grade tumors. This difference was significant (p 〈 0.05; two-tailed t-test). Similarly, the KD values (dissociation constant; nM) between the high (KD = 20.4 ± 1.3 nM) and low (KD = 14.3 ± 2.1 nM) grade gliomas were significantly different. A significant difference in binding site density (Bmax) between the two types of gliomas was also obtained in liquid scintillation measurements. The hot spot areas which showed the most intense binding of [3H]PK-11195 had KD of 24.5 ± 1.0 nM and Bmax of 6.2 ± 0.42 pmol/mg-tissue, values significantly higher (p 〈 0.05, two-tailed t-test) than those obtained when the entire tissue section was measured. The data on the Bmax/KD ratios presented here suggest that it might be possible to differentiate high from low grade gliomas in human by in vivo imaging with11 C-labelled PK-11195.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005933226966
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  • 8
    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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  • 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
    Serotonin Synthesis Increased in Terminals Four Days after Reserpine Treatment: An Autoradiographic Study in Rat Brain (1997)
    Springer
    Neurochemical research 22 (1997), S. 11-16 
    Details
    ISSN: 1573-6903
    Keywords: Serotonin synthesis ; reserpine ; rat brain ; autoradiography ; α-methyl-tryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The rate of 5-HT synthesis was determined in discrete rat brain regions 4 days after a single dose of reserpine (10 mg/kg) or reserpine carrier (controls), using an autoradiographic method with labelled α-methyl-L-tryptophan as a tracer. The results show that the rate of 5-HT synthesis was unchanged in the dorsal and median raphe, significantly decreased in the raphe magnus, and significantly increased in areas rich in serotonergic nerve terminals (i.e., hypothalamus, hippocampus, median geniculate body, parietal and visual cortices). An increase in tryptophan hydroxylase activity could account for the increase in the rate of serotonin synthesis seen in some regions. Since the 5-HT synthesis rate showed regional variability there seems to be a need for regional studies of the effect of drugs on the 5-HT synthesis. In addition, the 5-HT synthesis rate was not significantly different from that in controls in many of the brain regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1027360817407
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