Dopamine receptors: Effects of chronic L-dopa and bromocriptine treatment in an animal model of Parkinson's disease

M. B. Schneider, L. C. Murrin, R. F. Pfeiffer, J. D. Deupree

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31 Scopus citations

Abstract

Male albino rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra. Animals demonstrating contralateral rotations 2 weeks postoperatively with apomorphine (0.5 mg/kg i.p.) were treated with L-Dopa (55 mg/kg i.p.), bromocriptine (2 mg/kg i.p.), or polyethylene glycol (vehicle) every 12 h for 30 days. Striatal dopamine (DA) receptors were analyzed by Scatchard plot using 3H-spiroperidol (3H-SP) as ligand. 3,4-Dihydroxyphenylacetic acid (DOPAC) and DA were measured by use of high pressure liquid chromatography. 6-OHDA lesions produced a supersensitivity in striatal DA receptors. Chronic L-Dopa or bromocriptine treatment reversed this supersensitivity. Neither lesion nor drug treatment alone or together produced a significant change in affinity (K(D)) for 3H-SP. Drug treatment alone also had no effect on B(max). DA and DOPAC levels were reduced by greater than 98% in lesioned striata. Neither drug treatment affected DA or DOPAC levels as compared with controls. These results indicate that chronic administration of either bromocriptine or L-Dopa will reverse the DA receptor denervation supersensitivity in striatum seen following 6-OHDA lesion. This reversal may play a role in the clinical changes seen in Parkinson's disease patients following chronic use of these drugs.

Original languageEnglish (US)
Pages (from-to)247-257
Number of pages11
JournalClinical neuropharmacology
Volume7
Issue number3
StatePublished - Dec 1 1984

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ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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