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


OBJECTIVE
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.
Laszy
Judit
J
Department of Behavioural Pharmacology, Gedeon Richter Ltd, P.O.B. 27, Budapest, Hungary, 1475. j.laszy@richter.hu
Laszlovszky
István
I
Gyertyán
István
I
D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3; D012601:Scopolamine / Q000633:toxicity
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012601:Scopolamine