Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study.
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| Title: | Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. |
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| Authors: | Selvaraj, S, Turkheimer, F, Rosso, L, Faulkner, P, Mouchlianitis, E, Roiser, J P, McGuire, P, Cowen, P J, Howes, O |
| Source: | Molecular Psychiatry. Dec2012, Vol. 17 Issue 12, p1254-1260. 7p. 1 Black and White Photograph, 1 Diagram, 1 Chart, 2 Graphs. |
| Subjects: | Serotoninergic mechanisms, Neural transmission, Neurobehavioral disorders, Positron emission tomography, Citalopram, Antidepressants |
| Abstract: | Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT1A partial agonist radioligand [11C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [11C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BPND) were obtained by calculating total volumes of distribution (VT) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [11C]CUMI-101 BPND at postsynaptic 5-HT1A receptors in several cortical regions, but there was no change in binding at 5-HT1A autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [11C]CUMI-101 BPND (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [11C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT1A autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [11C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans. [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 83493850 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Measuring endogenous changes in serotonergic neurotransmission in humans: a [<superscript>11</superscript>C]CUMI-101 PET challenge study. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Selvaraj%2C+S%22">Selvaraj, S</searchLink><br /><searchLink fieldCode="AR" term="%22Turkheimer%2C+F%22">Turkheimer, F</searchLink><br /><searchLink fieldCode="AR" term="%22Rosso%2C+L%22">Rosso, L</searchLink><br /><searchLink fieldCode="AR" term="%22Faulkner%2C+P%22">Faulkner, P</searchLink><br /><searchLink fieldCode="AR" term="%22Mouchlianitis%2C+E%22">Mouchlianitis, E</searchLink><br /><searchLink fieldCode="AR" term="%22Roiser%2C+J+P%22">Roiser, J P</searchLink><br /><searchLink fieldCode="AR" term="%22McGuire%2C+P%22">McGuire, P</searchLink><br /><searchLink fieldCode="AR" term="%22Cowen%2C+P+J%22">Cowen, P J</searchLink><br /><searchLink fieldCode="AR" term="%22Howes%2C+O%22">Howes, O</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Dec2012, Vol. 17 Issue 12, p1254-1260. 7p. 1 Black and White Photograph, 1 Diagram, 1 Chart, 2 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Serotoninergic+mechanisms%22">Serotoninergic mechanisms</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+transmission%22">Neural transmission</searchLink><br /><searchLink fieldCode="DE" term="%22Neurobehavioral+disorders%22">Neurobehavioral disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Positron+emission+tomography%22">Positron emission tomography</searchLink><br /><searchLink fieldCode="DE" term="%22Citalopram%22">Citalopram</searchLink><br /><searchLink fieldCode="DE" term="%22Antidepressants%22">Antidepressants</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT1A partial agonist radioligand [11C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [11C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BPND) were obtained by calculating total volumes of distribution (VT) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [11C]CUMI-101 BPND at postsynaptic 5-HT1A receptors in several cortical regions, but there was no change in binding at 5-HT1A autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [11C]CUMI-101 BPND (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [11C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT1A autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [11C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/mp.2012.78 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 1254 Subjects: – SubjectFull: Serotoninergic mechanisms Type: general – SubjectFull: Neural transmission Type: general – SubjectFull: Neurobehavioral disorders Type: general – SubjectFull: Positron emission tomography Type: general – SubjectFull: Citalopram Type: general – SubjectFull: Antidepressants Type: general Titles: – TitleFull: Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Selvaraj, S – PersonEntity: Name: NameFull: Turkheimer, F – PersonEntity: Name: NameFull: Rosso, L – PersonEntity: Name: NameFull: Faulkner, P – PersonEntity: Name: NameFull: Mouchlianitis, E – PersonEntity: Name: NameFull: Roiser, J P – PersonEntity: Name: NameFull: McGuire, P – PersonEntity: Name: NameFull: Cowen, P J – PersonEntity: Name: NameFull: Howes, O IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 12 Text: Dec2012 Type: published Y: 2012 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 17 – Type: issue Value: 12 Titles: – TitleFull: Molecular Psychiatry Type: main |
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