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

• Published in: Neuroscience letters 2011-10, Vol.504 (3), p.209-214
• Main Authors: Voronova, Irina P, Naumenko, Vladimir S, Khramova, Galina M, Kozyreva, Tamara V, Popova, Nina K
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; 8-Hydroxy-2-(di-n-propylamino)tetralin - toxicity; Animals; Biguanides - pharmacology; Biguanides - toxicity; Body Temperature Regulation - drug effects; Body Temperature Regulation - physiology; Brain - metabolism; Carbon Dioxide - metabolism; Energy Metabolism - drug effects; Energy Metabolism - physiology; Hypothermia - chemically induced; Hypothermia - physiopathology; Lipid Metabolism; Male; Mice; Mice, Inbred CBA; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; Receptor, Serotonin, 5-HT1A - physiology; Receptors, Serotonin, 5-HT3 - physiology; Serotonin 5-HT1 Receptor Agonists - pharmacology; Serotonin 5-HT1 Receptor Agonists - toxicity; Serotonin 5-HT3 Receptor Agonists
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.09.024

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.