Behavioral and biochemical effects of the dopamine D3 receptor-selective ligand, 7-OH-DPAT, in the normal and the reserpine-treated rat

Eur J Pharmacol. 1994 Aug 1;260(2-3):177-81. doi: 10.1016/0014-2999(94)90335-2.

Abstract

In normal rats, the dopamine D3 receptor-selective ligand, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT), produced biphasic effects on spontaneous locomotor activity, i.e. suppression at low doses (0.06-0.25 mumol kg-1 s.c.), followed by a gradual increase in motor activity (1.0-4.0 mumol kg-1). The core temperature was decreased at these latter high doses only. The reserpine-induced (8.2 mumol kg-1 s.c.) increase in neostriatal 3,4-dihydroxyphenylalanine (DOPA) accumulation, following treatment with m-hydroxybenzylhydrazine-(NSD-1015) (475 mumol kg-1 i.p.), was dose dependently antagonized by 7-OH-DPAT in the dose range 0.02-4.0 mumol kg-1. The reserpine-induced suppression of spontaneous locomotor activity, however, was antagonized at higher doses only (1.0-4.0 mumol kg-1). Finally, there were no region-selective effects of 7-OH-DPAT on DOPA accumulation in the neostriatum. Thus, it appears that the dopamine D3 receptor-preferring ligand, 7-OH-DPAT, displays the profile of a dopamine D2 receptor agonist, pre- and postsynaptically.

MeSH terms

  • Analysis of Variance
  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Binding Sites
  • Body Temperature / drug effects
  • Dihydroxyphenylalanine / metabolism
  • Dose-Response Relationship, Drug
  • Hydrazines / pharmacology
  • Injections, Subcutaneous
  • Ligands
  • Male
  • Motor Activity / drug effects*
  • Neostriatum / drug effects*
  • Neostriatum / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D2*
  • Receptors, Dopamine D3
  • Reserpine / pharmacology*
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Drd3 protein, rat
  • Hydrazines
  • Ligands
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • Dihydroxyphenylalanine
  • Reserpine
  • 3-hydroxybenzylhydrazine
  • 7-hydroxy-2-N,N-dipropylaminotetralin