Trends in Neurosciences
Volume 23, Supplement 1, October 2000, Pages S101-S108
Journal home page for Trends in Neurosciences

Review
PET studies and motor complications in Parkinson's disease

https://doi.org/10.1016/S1471-1931(00)00016-1Get rights and content

Parkinson's disease (PD) patients with motor complications show a greater reduction in putamen [18F]dopa uptake on positron emission tomography (PET) compared with sustained responders to l-dopa, although individual ranges overlap considerably. This implies that, although loss of putamen dopamine storage predisposes motor complications in PD, it cannot be the only factor determining timing of onset. Additional PET studies suggest that loss of striatal dopamine storage capacity along with pulsatile exposure to exogenous l-dopa results in pathologically raised synaptic dopamine levels and deranged basal ganglia opioid transmission.This, rather than altered dopamine receptor binding, then causes inappropriate overactivity of basal ganglia-frontal projections, resulting in breakthrough involuntary movements.

References (80)

  • CrossA.J.

    Subtraction autoradiography of opiate receptor subtypes in human brain

    Brain Res.

    (1987)
  • PollardH.

    Localisation of opiate receptors and enkephalins in the rat striatum in relationship with the nigrostriatal dopamine system: lesion studies

    Brain Res.

    (1978)
  • MurrinL.C.

    Striatal opiate receptors: Pre- and postsynaptic localisation

    Life Sci.

    (1980)
  • ReisineT.D.

    Alterations in brain opiate receptors in Parkinson's disease

    Brain Res.

    (1979)
  • NisbetA.P.

    Preproenkephalin and preprotachykinin messenger-RNA expression in normal human basal ganglia and in Parkinson's disease

    Neuroscience

    (1995)
  • KoeppM.J.

    Focal cortical release of endogenous opioids during reading-induced seizures

    Lancet

    (1998)
  • NuttJ.G.

    Levodopa-induced dyskinesia: review, observations, and speculations

    Neurology

    (1990)
  • NuttJ.G. et al.

    The response to levodopa in Parkinson's disease: imposing pharmacological law and order

    Ann. Neurol.

    (1996)
  • LangstonJ.W.

    Chronic parkinsonism in humans due to a product of meperidine-analog synthesis

    Science

    (1983)
  • MouradianM.M.

    Pathogenesis of dyskinesias in Parkinson's disease

    Ann. Neurol.

    (1989)
  • BoyceS.

    Nigrostriatal damage is required for induction of dyskinesias by l-dopa in squirrel monkeys

    Clin. Neuropharrnacol.

    (1990)
  • PearceR.K.B.

    Altered striatal preproenkephalin mRNA levels in normal macaque monkeys (Macaca fascicularis) with dyskinesias induced by chronic l-dopa administration

    Br. J. Pharmacol.

    (1995)
  • FuxeK.

    Characterisation of normal and supersensitive dopamine receptors: effects of ergot drugs and neuropeptides

    J. Neural Transm.

    (1981)
  • PrzedborskiS.

    Unilateral MPTP-induced parkinsonism in monkeys — a quantitative autoradiographic study of dopamine-D1 and dopamine-D2 receptors and reuptake sites

    Neurochirurgie

    (1991)
  • LeesA.J. et al.

    Sustained bromocriptine therapy in previously untreated patients with Parkinson's disease

    J. Neurol. Neurosurg. Psychiatry

    (1981)
  • MontastrucJ.L.

    A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow-up

    J. Neurol. Neurosurg. Psychiatry

    (1994)
  • RinneU.K.

    Early treatment of Parkinson's disease with cabergoline delays the onset of motor complications

  • RascolO.

    Dyskinesia in Parkinson's disease: A 5-year study of ropinirole versus levodopa

    New Engl. J. Med.

    (2000)
  • BlanchetP.

    Differential effect of selective D-1 and D-2-dopamine receptor agonists on levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed monkeys

    J. Pharmacol. Exp. Ther.

    (1993)
  • PlayfordE.D. et al.

    In vivo and in vitro studies of the dopamine system in movement disorders

    Cerebrovasc. Brain Metab. Rev.

    (1992)
  • HaberS. et al.

    The comparative distribution of enkephalin, dynorphin, and substance P in the human globus pallidus and basal forebrain

    Neuroscience

    (1985)
  • PenneyJ.B. et al.

    Striatal inhomogeneities and basal ganglia function

    Mov. Disord.

    (1986)
  • EngbergT.M.

    Levodopa replacement therapy alters enzyme activities in striaturn and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats

    Brain Res.

    (1991)
  • LavoieB.

    Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys

    Can. J. Neurol. Sci.

    (1991)
  • HenryB. et al.

    Potential of opioid antagonists in the treatment of levodopa-induced dyskinesias in Parkinson's disease

    Drugs and Aging

    (1996)
  • LozanoA.M.

    Neuronal recordings in Parkinson's disease patients with dyskinesias induced by apomorphine

    Ann. Neurol.

    (2000)
  • FirnauG.

    Cerebral metabolism of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine in the primate

    J. Neurochem.

    (1987)
  • TedroffJ.

    Cerebral uptake and utilisation of therapeutic [β-11C]-l-DOPA in Parkinson's disease measured by positron emission tomography

  • KuwabaraH.

    Human striatal l-dopa decarboxylase activity estimated in vivo using 6-[18F]fluorodopa and positron emission tomography: error analysis and application to normal subjects

    J. Cereb. Blood Flow Metab.

    (1993)
  • BrooksD.J.

    Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

    Ann. Neural.

    (1990)
  • Cited by (28)

    • Long-term treatment with l-DOPA and an mGlu5 receptor antagonist prevents changes in brain basal ganglia dopamine receptors, their associated signaling proteins and neuropeptides in parkinsonian monkeys

      2014, Neuropharmacology
      Citation Excerpt :

      There is no clear consensus in the PD literature concerning relation between changes in LID and D1 receptors. D1 receptors were reported to be similar in PD patients whether treated or not with l-DOPA (Shinotoh et al., 1993) or decreased with long-term l-DOPA as measured by positron emission tomography (PET) (Brooks, 2000). In primates, striatal D1 receptor specific binding was reported to remain unchanged or increased after MPTP lesion (Alexander et al., 1993; Calon et al., 1995; Gagnon et al., 1990, 1995; Goulet et al., 2000; Guigoni et al., 2005).

    • Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson's disease

      2010, Parkinsonism and Related Disorders
      Citation Excerpt :

      The pathophysiology underlying this treatment-related complication is still not fully understood, but converging evidence points towards a pathologically raised volatility of synaptic striatal dopamine levels [20]. Levodopa-induced dyskinesias are associated with higher peaks of pulsatile dopamine transmission in the striatum [21] which seems to be positively correlated with disease duration [22]. Increased levels of regional activity in premotor and dorsal prefrontal cortices, as described here and in a study measuring regional blood flow during levodopa-related dyskinesias [23] can be regarded as a plausible downstream effect of increasingly overstimulated striato-frontal projections.

    • SPECT and PET in atypical parkinsonism

      2010, PET Clinics
      Citation Excerpt :

      This finding has provided both a rationale for symptomatic therapy as well as a target for imaging agents. There have been at least 3 different presynaptic dopaminergic targets that are used successfully to interrogate the dopamine system, with several radioligands for each: the dopamine transporter (123I-FP-CIT [DaTSCAN] and many others),14 the vesicular transporter (11C-VMAT2, 18F-AV-133),15 and dopamine metabolism (18F-dopa) (Fig. 1).16,17 Although each of these targets represents a different aspect of presynaptic dopamine function, there exists now several decades' worth of research and clinical application in assessing dopamine system changes with these targets to differentially diagnose, monitor, and screen patients with movement disorders.

    • Corticobasal degeneration: clinical aspects

      2008, Handbook of Clinical Neurology
      Citation Excerpt :

      The most specific feature was temporal atrophy, observed in CBD but not in PSP or CJD (Josephs et al., 2004a). Functional imaging, using PET and SPECT, shows a global reduction in cerebral blood flow/metabolism, with prefrontal, premotor, sensorimotor, parietal and superior temporal regions being particularly affected (Sawle et al., 1991; Brooks, 2000; Juh et al., 2005; Kreisler et al., 2005). The combination of cortical and subcortical features is often considered to be one of the most characteristic traits of CBD (Riley and Lang, 2000).

    View all citing articles on Scopus
    View full text