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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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The activity of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, was determined in the brain stem in active awake frogs, and frogs in three sleep-like states: with plastic muscle tone (SLS-1), with rigid muscle tone (SLS-2), and with relaxed muscle tone (SLS-3). Significant decrease in the enzyme activity has been found in frogs in SLS-1 and SLS-2 compared to awake animals. The development in frogs a cataleptic-like immobility after treating the animals with rhythmic lighting was accompanied with a decrease in the brain tryptophan hydroxylase activity. These results provide strong evidence for the involvement of the brain serotonin in frogs in the control of evolutionary ancient sleep-like states, probably by the regulation of muscle tone.

Marked changes were revealed in the activity of the key enzyme in serotonin biosynthesis, tryptophan hydroxylase (TPH), during entry into hibernation, hibernation, and arousal in ground squirrels (Citellus erythrogenys). An increase in TPH activity was found in the midbrain, hippocampus, and striatum during the prehibernation period in euthermic ground squirrels. A further increase in TPH activity was observed during the entry into hibernation. Significant elevation was found not only in potential TPH activity measured at the incubation temperature of 37 degrees C but also at incubation temperature of 7 degrees C, approximating the body temperature in hibernation. Vmax in the midbrain of hibernating animals was about 50% higher than in active ones without significant changes in Km. Thus, brain TPH maintains functionality during torpidity and is activated before the entry into hibernation. The results support the idea that brain serotonin is crucially involved in the transition to and the maintenance of the hibernation state.

An assay of tryptophane hydroxylase activity in brain was based on fluorometric measurement of serotonin after condensation with o-phthalic aldehyde in 10 N HCl. The method proved to be more sensitive and simple as compared with the previously reported technique and enabled to measure the enzyme activity in brain samples as little as 10 mg. The method is recommended for laboratory routine use.