Adenosine A2A receptor antagonism potentiates L-DOPA-induced turning behaviour and c-fos expression in 6-hydroxydopamine-lesioned rats

Eur J Pharmacol. 1997 Feb 26;321(2):143-7. doi: 10.1016/s0014-2999(96)00944-2.


In order to investigate the role of adenosine A2A receptor blockade on dopamine-mediated motor responses, contralateral turning behaviour and expression of the early-gene c-fos was evaluated in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway. SCH 58261, (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1 , 5-c]pyrimidine) a potent and selective antagonist of adenosine A2A receptors (5 mg/kg i.p.), induced a 70-fold increase in the contralateral turning behaviour induced by a low dose (2 mg/kg i.p.) of the dopamine precursor L-DOPA (L-3, 4-dihydroxyphenylalanine). Expression of c-fos as measured by Fos-like immunoreactivity after SCH 58261 plus L-DOPA was also potentiated as compared with L-DOPA alone, both in striatum and globus pallidus of the 6-hydroxydopamine-lesioned side of the brain. SCH 58261 induced a less marked potentiation (7-fold) of turning behaviour induced by dopamine D2 receptor stimulation with quinpirole, while Fos-like immunoreactivity in the striatum and globus pallidus was not affected. Previous studies have shown that SCH 58261 strongly potentiated dopamine D1 receptor-mediated responses. The results of the present study therefore indicate that the positive interaction between SCH 58261 and L-DOPA, in 6-hydroxydopamine-lesioned rats, is mainly due to an interaction with dopamine D1 receptors. The data also suggest that adenosine A2A receptor antagonists might be useful for potentiating the effects of L-DOPA in Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain Diseases / complications
  • Brain Diseases / metabolism*
  • Brain Diseases / physiopathology*
  • Dopamine Agonists / pharmacology
  • Drug Synergism
  • Gene Expression / drug effects
  • Genes, fos
  • Levodopa / pharmacology*
  • Male
  • Oxidopamine
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / immunology
  • Purinergic P1 Receptor Antagonists*
  • Pyrimidines / pharmacology*
  • Quinpirole / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Substantia Nigra / drug effects
  • Triazoles / pharmacology*


  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Dopamine Agonists
  • Proto-Oncogene Proteins c-fos
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D2
  • Triazoles
  • Quinpirole
  • Levodopa
  • Oxidopamine