Dopamine receptors status after unilateral nigral 6-OHDA lesion. Autoradiographic and in situ hybridization study in the rat brain

Mol Chem Neuropathol. May-Jun 1993;19(1-2):147-62. doi: 10.1007/BF03160175.

Abstract

The physiological effects of dopamine (DA) are mediated by several distinct receptor subtypes. The effects of unilateral nigral 6-hydroxydopamine (6-OHDA) lesions on DA receptors were investigated by receptor autoradiography using the D1 selective ligand [3H]SCH 23390 as well as the D2 ligand [3H]spiroperidol. mRNA distribution was studied by in situ hybridization. Lesioned rats were sacrificed at different time intervals. Receptor binding studies were performed on tissue sections using selective ligands. [35S]UTP labeled RNA probes were prepared from the different cDNA (D1, D2, D3) and used for in situ hybridization. A specific loss of receptor binding sites and mRNA hybridization was found in the lesioned substantia nigra pars compacta (SNc) at all times examined. Receptor binding studies revealed a different time-dependent increase in both D1 and D2 receptors. In situ hybridization showed that only D2 receptor mRNA increased in the caudate-putamen (CPu) of the lesioned side 15 d after 6-OHDA. No changes were observed in D1 and D3 receptor mRNA during the entire time-course.

MeSH terms

  • Animals
  • Autoradiography
  • Benzazepines / pharmacology
  • In Situ Hybridization
  • Male
  • Nerve Tissue Proteins / biosynthesis
  • Oxidopamine / toxicity*
  • RNA Probes
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / genetics
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Spiperone / pharmacology
  • Substantia Nigra / anatomy & histology
  • Substantia Nigra / drug effects*
  • Sulfur Radioisotopes

Substances

  • Benzazepines
  • Drd3 protein, rat
  • Nerve Tissue Proteins
  • RNA Probes
  • RNA, Messenger
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Sulfur Radioisotopes
  • Spiperone
  • Oxidopamine