Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe]
Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others,...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2015-01-01
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| Online Access: | http://f1000research.com/articles/4-23/v1 |
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| author | Kevin J. Black Marilyn L. Piccirillo Jonathan M. Koller Tiffany Hseih Lei Wang Mark A. Mintun |
| author_facet | Kevin J. Black Marilyn L. Piccirillo Jonathan M. Koller Tiffany Hseih Lei Wang Mark A. Mintun |
| author_sort | Kevin J. Black |
| collection | DOAJ |
| description | Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS). Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS. Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BPND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BPND voxel by voxel over the entire brain. Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa’s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects. Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa. |
| first_indexed | 2024-12-11T03:10:02Z |
| format | Article |
| id | doaj.art-964837fd58d24947b673ec4fd664804e |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-11T03:10:02Z |
| publishDate | 2015-01-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-964837fd58d24947b673ec4fd664804e2022-12-22T01:22:54ZengF1000 Research LtdF1000Research2046-14022015-01-01410.12688/f1000research.5672.16062Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe]Kevin J. Black0Marilyn L. Piccirillo1Jonathan M. Koller2Tiffany Hseih3Lei Wang4Mark A. Mintun5Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USATemple University, Philadelphia, PA, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USADepartment of Ophthalmology, University of Cincinnati, Cincinnati, OH, USADepartments of Psychiatry & Behavioral Sciences, and Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USAAvid Radiopharmaceuticals, Philadelphia, PA, USARationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS). Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS. Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BPND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BPND voxel by voxel over the entire brain. Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa’s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects. Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.http://f1000research.com/articles/4-23/v1Motor SystemsMovement DisordersNeurobiology of Disease & RegenerationNeuroimaging |
| spellingShingle | Kevin J. Black Marilyn L. Piccirillo Jonathan M. Koller Tiffany Hseih Lei Wang Mark A. Mintun Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] F1000Research Motor Systems Movement Disorders Neurobiology of Disease & Regeneration Neuroimaging |
| title | Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] |
| title_full | Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] |
| title_fullStr | Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] |
| title_full_unstemmed | Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] |
| title_short | Levodopa effects on [11C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] |
| title_sort | levodopa effects on 11c raclopride binding in the resting human brain v1 ref status indexed http f1000r es 4oe |
| topic | Motor Systems Movement Disorders Neurobiology of Disease & Regeneration Neuroimaging |
| url | http://f1000research.com/articles/4-23/v1 |
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