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Role of dopamine D3 receptors in thermoregulation: a reappraisal

Perachon, Sylvie1; Betancur, Catalina2; Pilon, Catherine1; Rostène, William2; Schwartz, Jean-Charles1; Sokoloff, Pierre1,3

Neuropharmacology and Neurotoxicology

Dopamine agonist-induced hypothermia has been proposed to be mediated by the D3 receptor (D3R), as it is elicited by (+)7-OH-DPAT and antagonized by S 14297, two putative D3R-preferential ligands. Here we show, however, that S 14297 is a full and partial agonist at D3R and D2R, respectively. Hypothermia was induced in rats by agonists with potencies correlated with their D3R and D2R functional potencies, and was reversed by antagonists, with a rank order of potency typical of the D2R. Moreover, BP 897, a highly potent and selective but partial D3R agonist was inactive in producing hypothermia or reversing (+)7-OH-DPAT-induced hypothermia. (+)7-OH-DPAT was as potent and efficient in inducing hypothermia in wild-type as in D3R-deficient mice. Hence, our results suggest that hypothermia does not result from a selective stimulation of the D3R.

1Unité de Neurobiologie et Pharmacologie Moléculaire (INSERM U 109), Centre Paul Broca, 2ter rue d'Alésia, F-75014 Paris

2Unité d'imagerie Cellulaire des Neurorécepteurs et Physiopathologie Neuroendocrinienne (INSERM U 339), Hôpital St-Antoine, 184, rue du Faubourg St-Antoine, F-75571 Paris cedex 12, France

3Corresponding Author: Pierre Sokoloff

Acknowledgments: We thank Drs S. Fuchs and D. Accili for providing us with the D3 receptor knock-out mice.

Received 22 October 1999; accepted 3 November 1999

© 2000 Lippincott Williams & Wilkins, Inc.