scispace - formally typeset

Topic

Serotonin

About: Serotonin is a(n) research topic. Over the lifetime, 18222 publication(s) have been published within this topic receiving 748735 citation(s). The topic is also known as: 5-HT & thrombotonin.


Papers
More filters
Journal ArticleDOI
08 Aug 2003-Science
TL;DR: It is shown that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants, suggesting that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neuroGenesis in the hippocampus.
Abstract: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

3,913 citations

Journal ArticleDOI

2,357 citations

Journal Article
TL;DR: The results suggest that p -chlorophenylalanine may effect 5HT depletion by inhibiting the biosynthesis of this monoamine, possibly by blocking tryptophan hydroxylation.
Abstract: p -Chlorophenylalanine has been found to be a potent and selective depletor of brain serotonin (5HT) in mice, rats and dogs. Brain 5-hydroxy-3-indolylacetic acid (5HIAA) content was also depleted by the drug, but catecholamine concentrations were only slightly decreased. Peripheral stores of 5HT were also lowered. In rats, p -chlorophenylalanine reduced the normal increase in brain 5-hydroxyl-3-indolyl compounds following L-tryptophan loading (without apparently affecting tryptophan uptake into brain), completely prevented the increase in brain 5HT accompanying inhibition of monoamine oxidase by pargyline and blocked the increase in brain 5HIAA usually observed after reserpine treatment. p -Chlorophenylalanine slightly diminished the usual increase in brain 5HT in rats following 5-hydroxytryptophan (5HTP) administration, but decreased the rate of disappearance of excess 5HT and antagonized the increase in brain 5HIAA. p -Chlorophenylalanine did not inhibit monoamine oxidase or 5HTP-decarboxylase in vitro and exerted no effect on monoamine oxidase or 5HTP decarboxylase activity of rat tissues in vivo. In contrast, p -chlorophenylalanine inhibited liver tryptophan hydroxylase in vitro and strongly suppressed the tryptophan- and phenylalanine-hydroxylating capabilities of livers of rats treated with it. These results suggest that p -chlorophenylalanine may effect 5HT depletion by inhibiting the biosynthesis of this monoamine, possibly by blocking tryptophan hydroxylation. A blockade of uptake of amino acid precursor might also contribute to the effect of decreasing 5HT biosynthesis. The slow depletion (2-3 days) of brain 5HT induced by p -chlorophenylalanine suggests that an active metabolite might be formed. p -Chlorophenylpyruvic acid exerted essentially the same pharmacologic effects as the amino acid, but it cannot be ascertained at present whether it is the active metabolite because of the interconversion of α-amino acids and α-keto acids in vivo. p -Chlorophenethylamine may be excluded as the metabolite responsible for the action of p -chlorophenylalanine because of the brief duration of the amine in brain and the short lasting, nonselective decrease of both 5HT and norepinephrine produced by the amine. A study of structural variation in the phenylalanine series indicated a specific requirement of a single chlorine substituent in the para position for potent in vivo activity. Rats treated with p -chlorophenylalanine displayed few apparent signs, and certainly not sedation. p -Chlorophenylalanine did not block characteristic signs elicited by reserpine or tetrabenazine in rats. Accordingly, the central actions of reserpine and reserpine-like drugs may possibly be dissociated from both 5HT concentrations and the formation of new 5HT in brain.

1,747 citations

Journal Article
TL;DR: It is proposed that [3H]5-HT and[3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5- HT2 receptors, respectively.
Abstract: [3H]5-Hydroxytryptamine (5-HT), [3H]lysergic acid diethylamide (LSD) and [3H]spiroperidol bind to membranes from the rat frontal cerebral cortex in a manner indicating a selective interaction with serotonin receptors. Differential drug potencies in competing for [3H]5-HT and [3H]spiroperidol binding sites suggest that these two [3H]ligands respectively label two distinct populations of receptors, while [3H]LSD labels both the [3H]5-HT and [3H]spiroperidol sites. After incubation of brain membranes with 30 nM spiroperidol, drug specificity of the residual [3H]LSD binding resembles that of receptors labeled by [3H]5-HT. Conversely, drug effects on [3H]LSD binding in the presence of 300 nM 5-HT resemble effects with [3H]spiroperidol. We propose that [3H]5-HT and [3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5-HT2 receptors, respectively. [3H]LSD appears to bind to both receptors to a similar extent.

1,348 citations


Network Information
Related Topics (5)
Dopamine

45.7K papers, 2.2M citations

95% related
Agonist

53.7K papers, 1.9M citations

90% related
Glutamate receptor

33.5K papers, 1.8M citations

90% related
Stimulation

40.1K papers, 1.4M citations

88% related
Hippocampal formation

30.6K papers, 1.7M citations

88% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20226
2021278
2020290
2019313
2018287
2017326