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

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.

• Authors: Judit Laszy, István Laszlovszky, István Gyertyán
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 179 Issue 3 Pg. 567-75 (May 2005) ISSN: 0033-3158 [Print] Germany
• PMID: 15619116 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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