Dissociation of metabolic and hemodynamic levodopa responses in the 6-hydroxydopamine rat model
Lerner, Renata P. ; Bimpisidis, Zisis LU ; Agorastos, Stergiani ; Scherrer, Sandra ; Dewey, Stephen L. ; Cenci Nilsson, Angela LU
and Eidelberg, David
(2016)
In Neurobiology of Disease
96.
p.31-37
- Abstract
Dissociation of vasomotor and metabolic responses to levodopa has been observed in human subjects with Parkinson's disease (PD) studied with PET and in autoradiograms from 6-hydroxydopamine (6-OHDA) rat. In both species, acute levodopa administration was associated with increases in basal ganglia cerebral blood flow (CBF) with concurrent reductions in cerebral metabolic rate (CMR) for glucose in the same brain regions. In this study, we used a novel dual-tracer microPET technique to measure CBF and CMR levodopa responses in the same animal. Rats with unilateral 6-OHDA or sham lesion underwent sequential 15O-water (H2 15O) and 18F-fluorodeoxyglucose (FDG) microPET to map CBF and CMR following... (More)
Dissociation of vasomotor and metabolic responses to levodopa has been observed in human subjects with Parkinson's disease (PD) studied with PET and in autoradiograms from 6-hydroxydopamine (6-OHDA) rat. In both species, acute levodopa administration was associated with increases in basal ganglia cerebral blood flow (CBF) with concurrent reductions in cerebral metabolic rate (CMR) for glucose in the same brain regions. In this study, we used a novel dual-tracer microPET technique to measure CBF and CMR levodopa responses in the same animal. Rats with unilateral 6-OHDA or sham lesion underwent sequential 15O-water (H2 15O) and 18F-fluorodeoxyglucose (FDG) microPET to map CBF and CMR following the injection of levodopa or saline. A subset of animals was separately scanned under ketamine/xylazine and isoflurane to compare the effects of these anesthetics. Regardless of anesthetic agent, 6-OHDA animals exhibited significant dissociation of vasomotor (ΔCBF) and metabolic (ΔCMR) responses to levodopa, with stereotyped increases in CBF and reductions in CMR in the basal ganglia ipsilateral to the dopamine lesion. No significant changes were seen in sham-lesioned animals. These data faithfully recapitulate analogous dissociation effects observed previously in human PD subjects scanned sequentially during levodopa infusion. This approach may have utility in the assessment of new drugs targeting the exaggerated regional vasomotor responses seen in human PD and in experimental models of levodopa-induced dyskinesia.
(Less)
- author
- Lerner, Renata P.
; Bimpisidis, Zisis
LU
; Agorastos, Stergiani
; Scherrer, Sandra
; Dewey, Stephen L.
; Cenci Nilsson, Angela
LU
and Eidelberg, David
- organization
- publishing date
- 2016-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cerebral blood flow, Glucose metabolism, Levodopa treatment, MicroPET, Parkinson's disease
- in
- Neurobiology of Disease
- volume
- 96
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:84983378556
- pmid:27544483
- wos:000388058900004
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2016.08.010
- language
- English
- LU publication?
- yes
- id
- ac86c839-f313-4090-8b38-f12e1f94f027
- date added to LUP
- 2016-10-12 13:00:14
- date last changed
- 2024-06-14 15:29:04
@article{ac86c839-f313-4090-8b38-f12e1f94f027,
abstract = {{<p>Dissociation of vasomotor and metabolic responses to levodopa has been observed in human subjects with Parkinson's disease (PD) studied with PET and in autoradiograms from 6-hydroxydopamine (6-OHDA) rat. In both species, acute levodopa administration was associated with increases in basal ganglia cerebral blood flow (CBF) with concurrent reductions in cerebral metabolic rate (CMR) for glucose in the same brain regions. In this study, we used a novel dual-tracer microPET technique to measure CBF and CMR levodopa responses in the same animal. Rats with unilateral 6-OHDA or sham lesion underwent sequential <sup>15</sup>O-water (H<sub>2</sub> <sup>15</sup>O) and <sup>18</sup>F-fluorodeoxyglucose (FDG) microPET to map CBF and CMR following the injection of levodopa or saline. A subset of animals was separately scanned under ketamine/xylazine and isoflurane to compare the effects of these anesthetics. Regardless of anesthetic agent, 6-OHDA animals exhibited significant dissociation of vasomotor (ΔCBF) and metabolic (ΔCMR) responses to levodopa, with stereotyped increases in CBF and reductions in CMR in the basal ganglia ipsilateral to the dopamine lesion. No significant changes were seen in sham-lesioned animals. These data faithfully recapitulate analogous dissociation effects observed previously in human PD subjects scanned sequentially during levodopa infusion. This approach may have utility in the assessment of new drugs targeting the exaggerated regional vasomotor responses seen in human PD and in experimental models of levodopa-induced dyskinesia.</p>}},
author = {{Lerner, Renata P. and Bimpisidis, Zisis and Agorastos, Stergiani and Scherrer, Sandra and Dewey, Stephen L. and Cenci Nilsson, Angela and Eidelberg, David}},
issn = {{0969-9961}},
keywords = {{Cerebral blood flow; Glucose metabolism; Levodopa treatment; MicroPET; Parkinson's disease}},
language = {{eng}},
month = {{12}},
pages = {{31--37}},
publisher = {{Elsevier}},
series = {{Neurobiology of Disease}},
title = {{Dissociation of metabolic and hemodynamic levodopa responses in the 6-hydroxydopamine rat model}},
url = {{http://dx.doi.org/10.1016/j.nbd.2016.08.010}},
doi = {{10.1016/j.nbd.2016.08.010}},
volume = {{96}},
year = {{2016}},
}