Repeated reserpine administration up-regulates the transduction mechanisms of D1 receptors without changing the density of [3H]SCH 23390 binding

Cristina Missale, Enzo Nisoli, Paolo Liberini, Paola Rizzonelli, Maurizio Memo, Matilde Buonamici, Alessandro Rossi, PierFranco Spano

Research output: Contribution to journalArticlepeer-review

Abstract

Behavioural studies have shown that stimulation of D1 receptors, which is uneffective in normal rats, induced strong hypermotility in rats pretreated with reserpine for 5 days. On this basis, we investigated D1 receptor plasticity using the 5-day treatment with reserpine (1 mg/kg; s.c.) as an experimental model. The function of striatal D1 receptors was determined both in binding studies with [3H]SCH 23390 and by measuring formation of cAMP in response to the selective agonist, SKF 82526. The results indicate that the responsiveness of adenylate cyclase (AC) to D1 receptor stimulation was markedly increased after reserpine administration, while no significant changes were found in [3H]SCH 23390 binding site density. Moreover, formation of cAMP after stimulation of Gs protein with GppNHp was markedly enhanced in dopamine (DA)-depleted rats; the responsiveness of AC to forskolin, which directly stimulates the AC catalytic unit, was not affected by reserpine administration. These data indicate that reserpine-induced D1 receptor up-regulation is apparently mediated by a marked enhancement of the coupling efficiency of Gs protein, suggesting that the D1 behavioral supersensitivity does not correlate with the density of D1 receptors, but is reflected by a selective up-regulation of their transduction mechanisms.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalBrain Research
Volume483
Issue number1
DOIs
Publication statusPublished - Mar 27 1989

Keywords

  • Adenylate cyclase
  • D receptor
  • Reserpine
  • Striatum
  • Supersensitivity
  • [H]SCH 23390 binding

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Repeated reserpine administration up-regulates the transduction mechanisms of D1 receptors without changing the density of [3H]SCH 23390 binding'. Together they form a unique fingerprint.

Cite this