Role of dopamine D3 receptors in thermoregulation: a reappraisal

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.