| 15033384 |
Hedlund PB, Kelly L, Mazur C, Lovenberg T, Sutcliffe JG, Bonaventure P: 8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents. Eur J Pharmacol. 2004 Mar 8;487(1-3):125-32.
Studies using selective drugs and knockout mice have demonstrated that the 5-HT (7) receptor plays an instrumental role in serotonin-induced hypothermia. There is also evidence supporting an involvement of the 5-HT (1A) receptor, although mainly from studies using 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT (1A/7) receptor agonist. Here we studied the effects of 8-OH-DPAT and selective antagonists for the 5-HT (1A) and 5-HT (7) receptors on body temperature in rats, wild-type (5-HT (7)(+/+)) mice and knockout (5-HT (7)(-/-)) mice. At lower doses (0.3-0.6 mg/kg, i.p.), 8-OH-DPAT decreased body temperature in 5-HT (7)(+/+) mice but not in 5-HT (7)(-/-) mice. At a higher dose (1 mg/kg, i.p.) 8-OH-DPAT induced hypothermia in both 5-HT (7)(-/-) and 5-HT (7)(+/+) mice. The 5-HT (1A) receptor antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl) piperazine-1-yl)-2-phenylpropanamid e (WAY-100135) (10 mg/kg, i.p.) inhibited the effect of 8-OH-DPAT at all doses in rats and mice. In 5-HT (7)(+/+) mice the selective 5-HT (7) receptor antagonist (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl) pyrrolidine-1-sulfonyl) phenol (SB-269970) (10 mg/kg, i.p.) fully inhibited the hypothermia induced by 0.3 mg/kg 8-OH-DPAT, but not that of higher doses. In rats, SB-269970 caused a 60% inhibition of the hypothermia induced by 0.3 mg/kg 8-OH-DPAT. Thus, both 5-HT (7) and 5-HT (1A) receptors are involved in a complex manner in thermoregulation, with the 5-HT (7) receptor being more important at lower, possibly more physiological, concentrations. |
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