Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms.

Sabatini, Umberto; Rascol, Olivier; Celsis, Pierre; Houin, Georges; Rascol, A; Marc-Vergnes, Jean-Pierre; Jl, Montastruc

doi:10.1111/j.1365-2125.1991.tb03886.x

Cited by 20 publications

(14 citation statements)

References 35 publications

(63 reference statements)

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“…Sabatini and colleagues [29], using xenon 133 washout and single-photon emission computed tomography (SPECT), studied a group of apomorphine-naive patients in contrast to our chronically exposed subjects. They found that apomorphine significantly increased global CBF.…”

Section: Apomorphine Effect On Global Cerebral Blood Flowmentioning

confidence: 98%

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

Jenkins

Fernández

Playford

et al. 1992

Annals of Neurology

395

197

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Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.

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Section: Apomorphine Effect On Global Cerebral Blood Flowmentioning

confidence: 98%

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

Jenkins

Fernández

Playford

et al. 1992

Annals of Neurology

395

197

View full text Add to dashboard Cite

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“…rCBF remains proportional to regional cerebral metabolic rate (rCMR) under various conditions (McCulloch et al, 1982a;Beck et al, 1986;Tuor et al, 1986); thus, quantitative images of rCBF only need to be scaled to reflect rCMR. Dopaminergics usually do not affect the global CBF/CMR ratio (Berntman et al, 1976(Berntman et al, , 1978McCulloch and Harper, 1977;McCulloch et al, 1978McCulloch et al, , 1982aMcCulloch and Edvinsson, 1980;Azuma et al, 1988;Sharkey et al, 1991), but certain drugs can change it (Ingvar et al, 1983;Leenders et al, 1985;Tuor et al, 1986;Beck et al, 1988;Sabatini et al, 1991). This raises the question of whether U91356a alters the vasculature to decrease global CBF or whether it decreases neuronal activity in large areas of brain.…”

Section: Discussionmentioning

confidence: 98%

“…Also, in our study domperidone did not prevent the global fall in CBF. Domperidone does not affect central metabolism (Palacios and Wiederhold, 1987), but can block a disproportionate, presumably vascular, change in rCBF after apomorphine (Sabatini et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo autoradiography gives precise anatomic detail (von Essen et al, 1980;Jauzac et al, 1982;McCulloch, 1982;McCulloch et al, 1982a,b,c;Wiederhold, 1984, 1985;Pizzolato et al, 1984Pizzolato et al, , 1985aPizzolato et al, ,b, 1987Wooten, 1986, 1987;Mori et al, 1989;Engber et al, 1990;Russo et al, 1991;Stein and Fuller, 1992;Tarazi et al, 1993), whereas PET and other imaging techniques allow in vivo studies using stimulants (Mathew and Wilson, 1989;Daniel et al, 1991;Pearlson et al, 1993), LDOPA (Rougemont et al, 1984;Henriksen and Boas, 1985;Leenders et al, 1985;Perlmutter and Raichle, 1985;Melamed et al, 1986;Montastruc et al, 1987;Rotrosen 1987;Kobari et al, 1992Kobari et al, , 1995, nonspecific dopamine agonists (Cleghorn et al, 1991;Sabatini et al, 1991;Grasby et al, 1993;Rascol et al, 1993;Kapur et al, 1994), and nonselective D 2 -like agonists (Celsis et al, 1988;Perlmutter, 1995). D 2 -like antagonists, although less relevant to this study, also have been studied extensively .…”

Section: Abstract: Globus Pallidus; Dopamine D 2 Receptor; Positron mentioning

confidence: 99%

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PET Measurement of Dopamine D₂Receptor-Mediated Changes in Striatopallidal Function

1997

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This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D 2 receptors. We hypothesized that a D 2 agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H 2 15 O and arterial sampling in six baboons before and after intravenous administration of the selective D 2 agonist U91356a. We also tested whether the response to U91356a was modified by previous acute administration of various antagonists. Another baboon had serial measurements of blood flow under identical conditions, but received no dopaminergic drugs. In all animals that received U91356a, pallidal flow decreased in a dose-related manner. Global CBF had a similar response, but the decline in pallidal flow was greater in magnitude and remained significant after accounting for the global effect. A D 2 antagonist, but not antagonists of D 1 , serotonin-2, or peripheral D 2 receptors, prevented this decrease. This work demonstrates and validates an in vivo measure of the sensitivity of D 2 -mediated basal ganglia pathways. It also supports the hypothesis that activation of the indirect striatopallidal pathway, previously demonstrated using nonselective D 2 -like agonists, can be mediated specifically by D 2 receptors. We speculate that the U91356a-PET technique may prove useful in detecting functional abnormalities of D 2 -mediated dopaminergic function in diseases such as parkinsonism, dystonia, Tourette syndrome, or schizophrenia.

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“…In particular, activation CBF studies may demonstrate functional abnormalities which are undetectable under resting conditions (Di Piero et al 1990) and show cerebral areas rsponsible for vicariant functions after the primary circuit is destroyed (Chollet et al 1991), as well as shed light on the effects of drugs on specific brain functions (Sabatini et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography

et al. 1992

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We applied the technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) split-dose method in order to evaluate the feasibility of assessing cerebral blood flow (CBF) changes with single photon emission tomography (SPET) during a motor activation task. Eleven normal subjects were studied using the Tomomatic 564 (Medimatic, DK). Five subjects were studied twice at rest and 6 subjects at rest and during a motor task performance (finger opposition movements). A total of 28 mCi of 99mTc-HMPAO was injected in 2 doses with a 1:3 ratio. The first scan was obtained after injection of 7 mCi at rest in all subjects. The second scan was obtained a few minutes later, after injection of the remaining dose (21 mCi), under similar resting conditions or during a motor task performance. The mean brain uptake was proportional to the amount of tracer injected and to the acquisition time for both the first scan (5263 +/- 1266 counts x mCi x min) and the second (5034.4 +/- 966 counts x mCi x min). The grey/white matter ratio was 1.67 +/- 0.019 and 1.67 +/- 0.097 for the two scans, respectively. A three-way analysis of variance (ANOVA) for repeated measure showed no significant effects of side, slice and region of interest (ROI) on the CBF in the 5 subjects studied twice at rest, and the mean regional CBF change was -0.2% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

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Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms.

Cited by 20 publications

References 35 publications

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

PET Measurement of Dopamine D₂Receptor-Mediated Changes in Striatopallidal Function

Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography

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Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms.

Cited by 20 publications

References 35 publications

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine

PET Measurement of Dopamine D2Receptor-Mediated Changes in Striatopallidal Function

Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography

Contact Info

Product

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About

PET Measurement of Dopamine D₂Receptor-Mediated Changes in Striatopallidal Function