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Continuous Dopaminergic Stimulation in Parkinson’s Disease pp 161–175Cite as

Receptor changes during chronic dopaminergic stimulation

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Part of the book series: Journal of Neural Transmission ((NEURAL SUPPL,volume 27))

Summary

The underlying cause of the long term complications of L-DOPA or dopamine agonist therapy in Parkinson’s disease remains unknown. Previous studies of repeated administration of L-DOPA or bromocriptine to rodents have shown increases, decreases or no change in brain dopaminergic activity. For this reason we have re-examined the effects of chronic L-DOPA or dopamine agonist administration on brain dopamine receptor function in rats.

Repeated intraperitoneal administration of L-DOPA to rats for 21 days followed by 3 days drug withdrawal caused an enhancement of apomorphine- induced stereotypy but no apparent alteration in striatal dopamine receptor numbers or affinity (as judged by 3H-spiperone; 3H-NPA and 3H-piflutixol binding).

Chronic oral administration of L-DOPA plus carbidopa to rats for one year was without effect on apomorphine-induced stereotypy or striatal D-2 dopamine receptors. Similarly, no effects were observed on striatal dopamine function following one year’s administration of bromocriptine. Pergolide produced an enhancement of apomorphine-induced stereotypy but a decrease in D-2 receptor density as judged by 3H-spiperone binding.

In rats with a unilateral 6-OHDA lesion of the medial forebrain bundle the oral administration of L-DOPA plus carbidopa for 4 weeks, followed by 4 days withdrawal, enhanced the rate of apomorphine-induced contraversive rotation.

It appears difficult, at least in rats, to manipulate striatal dopamine receptors with L-DOPA or dopamine agonist drugs. An enhancement of motor behaviour can occur in the presence of no change or a decrease in dopamine receptor numbers identified by in vitro ligand binding to tissue homogenates.

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Author notes

  1. C. D. Marsden

    Present address: University Department of Clinical Neurology, The National Hospital for Nervous Diseases, Queen Square, London, WC1N 3BG, UK

Authors and Affiliations

  1. MRC Movement Disorders Research Group, University Department of Neurology, London, UK

    Dr. P. Jenner, S. Boyce & C. D. Marsden

  2. Parkinson’s Disease Society Research Centre, Institute of Psychiatry and King’s College Hospital Medical School, London, UK

    Dr. P. Jenner, S. Boyce & C. D. Marsden

Authors
  1. Dr. P. Jenner
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  2. S. Boyce
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  3. C. D. Marsden
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Editor information

Editors and Affiliations

  1. Clinica Universitaria, Pamplona, Spain

    J. A. Obeso

  2. HA Klinische Forschung II, Schering AG, Berlin, Germany

    R. Horowski

  3. University Department of Clinical Neurology, The National Hospital for Nervous Diseases, London, UK

    C. D. Marsden

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© 1988 Springer-Verlag

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Jenner, P., Boyce, S., Marsden, C.D. (1988). Receptor changes during chronic dopaminergic stimulation. In: Obeso, J.A., Horowski, R., Marsden, C.D. (eds) Continuous Dopaminergic Stimulation in Parkinson’s Disease. Journal of Neural Transmission, vol 27. Springer, Vienna. https://doi.org/10.1007/978-3-7091-8954-2_14

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  • DOI: https://doi.org/10.1007/978-3-7091-8954-2_14

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-82034-6

  • Online ISBN: 978-3-7091-8954-2

  • eBook Packages: Springer Book Archive

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