Effects of the 5-HT7 receptor antagonist SB-269970 on rat hormonal and temperature responses to the 5-HT1A/7 receptor agonist 8-OH-DPAT.

The physiological function of 5-HT(7) receptors is not yet fully determined. This study was designed to characterize the involvement of 5-HT(7) receptor in rat body temperature regulation and in adrenocorticotropic hormone (ACTH) and corticosterone secretion. In the first part of our study, acute administration of SB-269970 (0.1-1 mg/kg, i.p.), a potent and selective 5-HT(7) receptors antagonist, dose-dependently prevented 5-HT(1A/7) receptor agonist 8-OH-DPAT (0.1 mg/kg, s.c.)-induced hypothermia and when the 5-HT(1A) receptor antagonist WAY-100,635 was co-injected with SB-269970, a reduction of the latter hypothermia was obtained in an additive manner. In contrast, 1 mg/kg (i.p.) of SB-269970 failed to prevent 8-OH-DPAT (0.5 mg/kg, s.c.)-induced increase of ACTH and corticosterone plasma levels. In conclusion, the present results unveil an additive effect of both 5-HT(1A) and 5-HT(7) receptors in core body temperature regulation.