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Dopamine receptor changes in response to prolonged treatment with L-dopa.

Abstract
Unilateral lesions of the nigro-striatal dopamine (DA) pathway induced contralateral rotations to apomorphine, increased (3H)-spiroperidol binding and enhanced the sensitivity of striatal adenylate cyclase to DA stimulation. Prolonged L-dopa administration counteracted the increased density of (3H)-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to DA and decreased the inhibitory effect of opiates on this enzyme. The apomorphine-induced contralateral rotations were also strongly potentiated. On the contrary the binding of (3H)-SCH-23390 was affected neither by DA nerve degeneration nor by chronic L-dopa treatment. These results suggest that DA-D1 and DA-D2 receptors are differently affected by prolonged L-dopa treatment. The biochemical changes of DA-D1 receptors associated with adenylate cyclase seem to be correlated with the enhanced behavioural responses to apomorphine and could be a consequence of a decreased opiate inhibitory tone on the enzyme. The increased supersensitivity of the DA-D1 receptors may play a role in the clinical changes seen in parkinsonian patients following chronic use of L-dopa.
AuthorsA Groppetti, C Flauto, E Parati, A Vescovi, L Rusconi, M Parenti
JournalJournal of neural transmission. Supplementum (J Neural Transm Suppl) Vol. 22 Pg. 33-45 ( 1986) ISSN: 0303-6995 [Print] Austria
PMID2946813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzazepines
  • Hydroxydopamines
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Levodopa
  • Spiperone
  • Sulpiride
  • Oxidopamine
  • Adenylyl Cyclases
  • Carbidopa
  • Apomorphine
  • Dopamine
Topics
  • Adenylyl Cyclases (metabolism)
  • Animals
  • Apomorphine (pharmacology)
  • Benzazepines (metabolism, pharmacology)
  • Carbidopa (pharmacology)
  • Corpus Striatum (drug effects)
  • Dopamine (physiology)
  • Hydroxydopamines (pharmacology)
  • Levodopa (pharmacology)
  • Male
  • Oxidopamine
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine (drug effects)
  • Receptors, Dopamine D1
  • Spiperone (metabolism)
  • Stereotyped Behavior (drug effects)
  • Substantia Nigra (physiology)
  • Sulpiride (pharmacology)

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