Central 5-HT3 receptor-induced hypothermia is associated with reduced metabolic rate and increased heat loss

Abstract

Activation of central 5-HT(3) receptors by the selective agonist m-CPBG (1-(3-chlorophenyl)biguanide hydrochloride, 40 nM i.c.v.) produced stronger hypothermic effect in mice than activation of 5-HT(1A) receptors by their agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propilamino)tetralin) injected by the same route at an equimolar dose. The hypothermic effect of m-CPBG was realized by influence on both the heat production and the heat loss: oxygen consumption and CO(2) expiration were decreased; heat dissipation determined by the tail skin temperature was increased. The heat loss effect of 5-HT(3) receptors was significantly shorter than the decrease in metabolism indicating the prevalent role of heat production decrease in 5-HT(3) receptor-induced deep and long-lasing hypothermia. In addition, the decrease in the respiratory exchange ratio (RER) was shown suggesting that the activation of the 5-HT(3) receptors switched metabolism to prevalent use of lipids as the main energetic substrate. 5-HT(1A) receptor agonist 8-OH-DPAT (40 nM i.c.v.) produced less depressing effect on general metabolism: a decrease in oxygen consumption and CO(2) excretion began later and was not so deep as after m-CPBG administration. Heat-loss effect of 5-HT(1A) receptors activation was not observed. In contrast to m-CPBG effect, RER after 5-HT(1A) receptors activation raised immediately after injection and then gradually decreased to the values observed in m-CPBG-treated mice. Obtained results show that activation of central 5-HT(3) receptors are more effective in hypothermia induction due to marked decrease in thermogenesis and increase in heat loss.