Continuous and intermittent levodopa differentially affect basal ganglia function

Continuous and intermittent levodopa differentially affect basal ganglia function The effects of continuous and intermittent levodopa treatment on behavioral and biochemical indexes of basal ganglia function were compared in rats with unilateral 6‐hydroxydopamine lesions of the nigrostriatal dopamine pathway. Animals treated for 30 days with intermittent levodopa exhibited behavioral sensitization manifested by an enhanced rotational response to apomorphine; the rotational response of rats treated with an equivalent dose of levodopa by continuous infusion did not differ from that of saline‐treated controls. Dopamine receptor up‐regulation in the denervated striatum relative to the intact striatum was statistically significant for D1 but not D2 receptors: This asymmetry in dopamine receptor levels was diminished following intermittent levodopa treatment. Glutamic acid decarboxylase activity, modestly elevated in all groups in the denervated striatum relative to the intact striatum, increased substantially over control values bilaterally as a result of intermittent, but not continuous, levodopa treatment. These findings suggest a relation between the schedule of chronic levodopa administration and the development of behavioral sensitization, possibly as a consequence of alterations in neuronal systems located downstream from striatal dopamine receptors. The behavioral sensitization induced by chronic, intermittent dopaminomimetic treatment may serve as a model for motor fluctuations in Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Continuous and intermittent levodopa differentially affect basal ganglia function

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Publisher
Wiley
Copyright
Copyright © 1989 The American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
D.O.I.
10.1002/ana.410250509
Publisher site
See Article on Publisher Site

Abstract

The effects of continuous and intermittent levodopa treatment on behavioral and biochemical indexes of basal ganglia function were compared in rats with unilateral 6‐hydroxydopamine lesions of the nigrostriatal dopamine pathway. Animals treated for 30 days with intermittent levodopa exhibited behavioral sensitization manifested by an enhanced rotational response to apomorphine; the rotational response of rats treated with an equivalent dose of levodopa by continuous infusion did not differ from that of saline‐treated controls. Dopamine receptor up‐regulation in the denervated striatum relative to the intact striatum was statistically significant for D1 but not D2 receptors: This asymmetry in dopamine receptor levels was diminished following intermittent levodopa treatment. Glutamic acid decarboxylase activity, modestly elevated in all groups in the denervated striatum relative to the intact striatum, increased substantially over control values bilaterally as a result of intermittent, but not continuous, levodopa treatment. These findings suggest a relation between the schedule of chronic levodopa administration and the development of behavioral sensitization, possibly as a consequence of alterations in neuronal systems located downstream from striatal dopamine receptors. The behavioral sensitization induced by chronic, intermittent dopaminomimetic treatment may serve as a model for motor fluctuations in Parkinson's disease.

Journal

Annals of NeurologyWiley

Published: May 1, 1989

References

  • Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, part II
    Mouradian, Mouradian; Juncos, Juncos; Fabbrini, Fabbrini
  • Increased or decreased locomotor response in rats following repeated administration of apomorphine depends on dosage interval
    Castro, Castro; Abreu, Abreu; Calzadilla, Calzadilla; Rodriguez, Rodriguez
  • A rapid radiochemical method for the determination of choline acetyltransferase
    Fonnum, Fonnum
  • Levodopa‐induced receptor hypersensitivity
    Klawans, Klawans; Goetz, Goetz; Nausieda, Nausieda; Weiner, Weiner
  • GABA‐mimetic drugs enhance apomorphine induced contralateral turning in rats with unilateral nigrostriatal dopamine denervation: implication for the therapy of Parkinson's disease
    Bennett, Bennett; Ferrari, Ferrari; Cruz, Cruz
  • Choline high‐affinity uptake and metabolism and choline acetyltransferase activity in the striatum of rats chronically treated with neuroleptics
    Pedata, Pedata; Sorbi, Sorbi; Pepeu, Pepeu
  • Intravenous lisuride corrects oscillations of motor performance in Parkinson's disease
    Obeso, Obeso; Luquin, Luquin; Martinez‐Lage, Martinez‐Lage

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