Dopamine D1 and D2 receptors visualized in MPTP treated C57 mice by in vitro autoradiography: lack of evidence of receptor modifications in parkinsonian mice

Pharmacol Toxicol. 1989 Sep;65(3):169-74. doi: 10.1111/j.1600-0773.1989.tb01150.x.

Abstract

The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on D1 and D2 dopamine receptors was assayed using in vitro quantitative autoradiography. D1 receptor subtype was labeled using 1 nM of 3H-SCH 23390 and D2 receptor subtype was labeled using 0.4 nM of 3H-spiroperidol. The results are compared to the effect of MPTP on the striatal levels of dopamine and its metabolites, in BL C57 mice. While 2 and 5 doses of MPTP 30 mg/kg/day intraperitoneally reduced the content of striatal dopamine and its metabolites, no modifications were detected in D2 receptor subtype in any cerebral area studied. However, D1 receptors were reduced in the substantia nigra 24 hr after the last of 2 doses, but not later. We suggest a compensatory mechanism of the surviving dopaminergic neurones as well as the participation of spare receptors. This would explain the lack of receptor modification after the lesion obtained as seen by the striatal reduction of dopamine and metabolites content, after MPTP administration.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Autoradiography
  • Benzazepines / pharmacology
  • Brain / metabolism
  • Dopamine / metabolism
  • Homovanillic Acid / metabolism
  • MPTP Poisoning*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parkinson Disease, Secondary / physiopathology*
  • Receptors, Dopamine / drug effects*
  • Spiperone / pharmacology

Substances

  • Benzazepines
  • Receptors, Dopamine
  • 3,4-Dihydroxyphenylacetic Acid
  • Spiperone
  • Dopamine
  • Homovanillic Acid