Psychopharmacology

, Volume 179, Issue 3, pp 567–575

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

  • Judit Laszy
  • István Laszlovszky
  • István Gyertyán
Original Investigation

Abstract

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.

Keywords

Dopamine D3 Memory Water labyrinth Scopolamine FG-7142 Rat 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Judit Laszy
    • 1
  • István Laszlovszky
    • 2
  • István Gyertyán
    • 1
  1. 1.Department of Behavioural PharmacologyGedeon Richter LtdBudapestHungary
  2. 2.Department of Clinical ResearchGedeon Richter LtdBudapestHungary

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