Motor actions of 7-OH-DPAT in normal and reserpine-treated mice suggest involvement of both dopamine D2 and D3 receptors

Eur J Pharmacol. 1995 Apr 24;277(2-3):151-8. doi: 10.1016/0014-2999(95)00063-q.

Abstract

In non-habituated mice, 7-hydroxy-N,N-di-n-propylaminotetralin (7-OH-DPAT, 0.04-10 mg/kg s.c.) potently and rapidly suppressed species-typical behaviours and induced frozen postures, with only occasional evidence of weak behavioural stimulation occurring at 5-10 mg/kg. This inhibitory effect was reversed by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8-di-hydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 10 mg/kg i.p.). 7-OH-DPAT (3-10 mg/kg) did not reinstate locomotion in 4 h habituated mice, either when administered alone or in conjunction with a threshold dose of SKF 38393 (3 mg/kg). By contrast, 7-OH-DPAT (0.2-10 mg/kg) dose-dependently reversed the akinesia of 24 h reserpine-treated mice. This response was blocked by the dopamine D2 receptor antagonist raclopride (10 mg/kg i.p.), but not by the dopamine D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol hemimaleate (SCH 23390, 0.05 mg/kg i.p.), and was potentiated synergistically by coinjection of SKF 38393 (3 mg/kg). These and earlier data suggest the motor inhibitory effects of 7-OH-DPAT (low doses) in normal animals are mediated by dopamine autoreceptors (D2 and/or D3), whilst its motor stimulant actions in normal (high doses) and in dopamine-depleted, supersensitive animals, are mediated by dopamine D2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Analysis of Variance
  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Habituation, Psychophysiologic
  • Injections, Intraperitoneal
  • Mice
  • Motor Activity / drug effects*
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Reserpine / administration & dosage
  • Reserpine / pharmacology*
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Benzazepines
  • Dopamine Agonists
  • Drd3 protein, mouse
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Reserpine
  • 7-hydroxy-2-N,N-dipropylaminotetralin