Dopamine D3 receptor ligands show place conditioning effect but do not influence cocaine-induced place preference

Neuroreport. 2003 Jan 20;14(1):93-8. doi: 10.1097/00001756-200301200-00018.

Abstract

The importance of dopamine D3 receptors in reward related processes, especially in cocaine addiction, has been investigated extensively. However, in the reported studies a combination of different experimental conditions and different ligands have been used which renders the interpretation and comparison of the diverse results extremely difficult. Here, we report one comparative study investigating a wide range of dopamine D3 receptor ligands in one model of cocaine abuse: the place conditioning paradigm in rats. Of the antagonists tested, the moderately D3 selective nafadotride and the more selective SB-277011 did not produce any place conditioning effect while U-99194A caused place-preference. The most D3 selective agonist PD-128907, the less selective 7-OH-DPAT and the moderately selective partial agonist BP-897 all caused significant place aversion. None of the compounds influenced the cocaine-induced place preference. Results suggest the D3-preferring agonists could affect the reward mechanisms of the brain, however, modulation of D3 receptor function does not appear to be a significant mechanism for modifying the place conditioning effect of cocaine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Benzazepines / pharmacology
  • Benzopyrans / pharmacology
  • Cocaine / pharmacology
  • Cocaine / toxicity*
  • Conditioning, Classical / drug effects*
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists
  • Haloperidol / pharmacology
  • Indans / pharmacology
  • Male
  • Naphthalenes / pharmacology
  • Nitriles / pharmacology
  • Oxazines / pharmacology
  • Piperazines / pharmacology
  • Pyrrolidines / pharmacology
  • Quinolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Dopamine D3
  • Reinforcement, Psychology
  • Reward*
  • Spatial Behavior / drug effects*
  • Substance-Related Disorders / physiopathology*
  • Tetrahydroisoquinolines*
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Benzazepines
  • Benzopyrans
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Drd3 protein, rat
  • Indans
  • Naphthalenes
  • Nitriles
  • Oxazines
  • Piperazines
  • Pyrrolidines
  • Quinolines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • SB 277011
  • Tetrahydroisoquinolines
  • Tetrahydronaphthalenes
  • 3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol
  • (5,6-dimethoxyindan-2-yl)dipropylamine
  • BP 897
  • Cocaine
  • Haloperidol
  • nafadotride
  • 7-hydroxy-2-N,N-dipropylaminotetralin