Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats

Psychopharmacology (Berl). 2005 May;179(3):567-75. doi: 10.1007/s00213-004-2096-z. Epub 2004 Dec 24.


Rationale: The dopamine D3 receptor has been extensively studied in animal models of drug abuse and psychosis; however, less is known on its possible role in cognitive functions.

Objectives: This study investigated the effects of different D3 antagonists and a partial agonist on spatial learning performance in a water labyrinth test.

Methods: Rats had to swim through a labyrinth system by making correct directional turns at three choice-points. The number of errors was recorded in three daily trials for 3 days.

Results: D3 antagonists such as the highly selective SB-277011 (24 mg/kg p.o.) and RGH-1756 (1 mg/kg p.o.), the moderately selective U-99194A (12 mg/kg s.c.) and the selective partial D3 agonist BP-897 (1 mg/kg i.p.) all significantly attenuated the learning deficit caused by FG-7142. Against scopolamine-induced amnesia, SB-277011 (24 mg/kg p.o.) was equally potent in showing protective efficacy; however, two times higher dose levels of U-99194A (24 mg/kg s.c.) and RGH-1756 (2 mg/kg p.o.) were required to attenuate the scopolamine-induced impairment. In contrast to the full antagonists, against scopolamine-induced amnesia, the partial agonist BP-897 (2 mg/kg i.p.) was inactive, even at the two times higher dose level.

Conclusions: These data suggest that dopamine D3 receptor antagonists possess cognition-enhancing activity which may be of benefit in the treatment of cognitive dysfunction associated with several psychiatric disorders.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Dopamine Antagonists / pharmacology*
  • Dopamine Antagonists / therapeutic use*
  • Dopamine D2 Receptor Antagonists*
  • Learning / drug effects*
  • Learning / physiology
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / physiology
  • Receptors, Dopamine D3
  • Scopolamine / toxicity


  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Drd3 protein, rat
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Scopolamine