Receptor changes during chronic dopaminergic stimulation

  • P. Jenner
  • S. Boyce
  • C. D. Marsden
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 27)


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.


Dopamine Receptor Dopamine Agonist Dopamine Agonist Therapy Striatal Dopamine Receptor Spiperone Binding 
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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • P. Jenner
    • 1
    • 2
  • S. Boyce
    • 1
    • 2
  • C. D. Marsden
    • 1
    • 2
  1. 1.MRC Movement Disorders Research GroupUniversity Department of NeurologyLondonUK
  2. 2.Parkinson’s Disease Society Research CentreInstitute of Psychiatry and King’s College Hospital Medical SchoolLondonUK

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