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Receptor changes during chronic dopaminergic stimulation.

P Jenner1, S Boyce, C D Marsden

  • 1University Department of Neurology, Institute of Psychiatry, London, U.K.

Journal of Neural Transmission. Supplementum
|January 1, 1988
PubMed
Summary
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Long-term L-DOPA or dopamine agonist treatment for Parkinson's disease may not alter dopamine receptors in rats. Motor behavior improvements can occur despite unchanged or reduced receptor numbers, suggesting complex therapeutic mechanisms.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The long-term effects of L-DOPA and dopamine agonists on brain dopaminergic activity in Parkinson's disease are not fully understood.
  • Previous rodent studies show conflicting results regarding changes in dopaminergic activity after chronic drug administration.

Purpose of the Study:

  • To investigate the impact of chronic L-DOPA and dopamine agonist administration on dopamine receptor function in rats.
  • To determine if these treatments alter striatal dopamine receptor density or affinity.

Main Methods:

  • Rats received repeated intraperitoneal or oral administration of L-DOPA (with or without carbidopa) or dopamine agonists (bromocriptine, pergolide).
  • Apomorphine-induced stereotypy and contraversive rotation were measured.
  • Striatal dopamine receptor binding was assessed using radioligand assays (3H-spiperone, 3H-NPA, 3H-piflutixol).

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Main Results:

  • Short-term L-DOPA enhanced stereotypy but did not alter receptor numbers/affinity.
  • One-year L-DOPA/carbidopa or bromocriptine treatment had no effect on stereotypy or D-2 receptors.
  • Pergolide increased stereotypy but decreased D-2 receptor density.
  • L-DOPA/carbidopa enhanced rotation in lesioned rats.

Conclusions:

  • Striatal dopamine receptors are difficult to manipulate with L-DOPA or dopamine agonists in rats.
  • Enhanced motor behavior can occur independently of changes in receptor density detected by in vitro binding assays.