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

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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.

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Acknowledgements

The authors thank Mrs. Csilla Nagy and Mrs. Tünde Féth for their careful technical assistance.

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Authors and Affiliations

  1. Department of Behavioural Pharmacology, Gedeon Richter Ltd, P.O.B. 27, Budapest, Hungary, 1475

    Judit Laszy & István Gyertyán

  2. Department of Clinical Research, Gedeon Richter Ltd, P.O.B. 27, Budapest, Hungary, 1475

    István Laszlovszky

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  1. Judit Laszy
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Correspondence to Judit Laszy.

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Laszy, J., Laszlovszky, I. & Gyertyán, I. Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats. Psychopharmacology 179, 567–575 (2005). https://doi.org/10.1007/s00213-004-2096-z

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  • DOI: https://doi.org/10.1007/s00213-004-2096-z

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