title: 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.
authors.affiliation: Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, 4, Timakov Street, 630117 Novosibirsk, Russia.
authors.forename: Irina P
authors.initials: IP
authors.lastname: Voronova
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Naumenko
authors.forename: Galina M
authors.initials: GM
authors.lastname: Khramova
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Kozyreva
authors.forename: Nina K
authors.initials: NK
authors.lastname: Popova
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001645:Biguanides / Q000494:pharmacology* / Q000633:toxicity; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000633:toxicity; D058827:Serotonin 5-HT3 Receptor Agonists
chemical_list: D001645:Biguanides; D044406:Receptors, Serotonin, 5-HT3; D058825:Serotonin 5-HT1 Receptor Agonists; D058827:Serotonin 5-HT3 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D002245:Carbon Dioxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C065734:1-(3-chlorophenyl)biguanide