Pflügers Archiv

, Volume 377, Issue 3, pp 245–249 | Cite as

Elevating serotonin levels in brain with 5-hydroxytryptophan produces hypothermia in rats

  • M. T. Lin
  • C. F. Chow
  • Y. F. Chern
  • K. M. Wu
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology


The effect of the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) on the thermoregulatory responses of unanesthetized rats were assessed at three different ambient temperatures (Ta) of 8, 22 and 31°C. Intraperitoneal administration of either 5-HTP alone or 5-HTP plus R04-4602 (the peripheral decarboxylase inhibitor) produced dose-dependent hypothermia at bothTa's of 8 and 22°C. The hypothermia was brought about solely by a decrease in metabolic heat production at 8°CTa. At 22°CTa, the hypothermia was due to both a decrease in metabolic heat production and a increase in tail and footsole skin temperature. However, at 31°CTa, there were no changes in rectal temperature in response to either 5-HTP or 5-HTP plus R04-4602 application. The data suggest that an increase in 5-HT levels in brain decreases heat production and/or increase heat loss and leads to hypothermia in rats.

Key words

Brain serotonin Teperature regulation Peripheral decarboxylase inhibition 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amin, A. H., Crawford, B. B., Gaddum, J. H.: The distribution of substance P and 5-hydroxytryptamine in the central nervous system of the dog. J. Physiol. (Lond.)126, 596–618 (1954)Google Scholar
  2. Atack, C., Lindqvist, M.: Conjoint native and orthophthaldialdehydecondensate assay for the fluorimetric determination of 5-hydroxyindoles in brain. Naunyn-Schmiedeberg's Arch. Pharmacol.279, 267–284 (1973)Google Scholar
  3. Bartholini, G., Burkard, W. F., Pletscher, A., Bates, H. M.: Increase of cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature215, 852–853 (1967)Google Scholar
  4. Blight, J., Cottle, W. H., Maskrey, M.: Influence of ambient temperature on the thermoregulatory responses to 5-hydroxytryptamine, noradrenaline, and acetylcholine injected into the lateral cerebral ventricles of sheep, goats, and rabbits. J. Physiol. (Lond.)212, 377–392 (1971)Google Scholar
  5. Cooper, J. R., Bloom, F. E., Roth, R. H.: The biochemical basis of neuropharmacology. New York: Oxford University Press 1974Google Scholar
  6. Dickenson, A. H.: Neurons in raphe' nuclei of the rat responding to skin temperature. J. Physiol. (Lond.).256, 110p (1976)Google Scholar
  7. Eisenman, J. S.: Unit studies of brainstem projections to the preoptic area and hypothalamus. In: Recent studies in hypothalamic function (Lederis, K., Cooper, K. E., eds.), Basel: Karger 1974Google Scholar
  8. Feldberg, W., Lotti, V. J.: Temperature responses to monoamines and an inhibitor of MAO injected into the cerebral ventricles of rats. Br. J. Pharmacol. Chemother.31, 152–161 (1967)Google Scholar
  9. Francesconi, R. P., Mager, M.: Salicylate, tryptophan, and tyrosine hypothermia. Am. J. Physiol.228, 1431–1435 (1975)Google Scholar
  10. Gallager, D. W., Aghajanian, G. K.: Inhibition of firing of raphe neurons by tryptophan and 5-hydroxytryptophan: blockade by inhibiting serotonin synthesis with R04-4602. Neuropharmacology15, 149–156 (1976)Google Scholar
  11. Hellon, R. F.: Monoamines, Pyrogens and Cations: their action on central control of body temperature. Pharmacol. Rev.26, 289–321 (1975)Google Scholar
  12. Jahns, R.: Different projections of cutaneous thermal input to single units of the midbrain raphe nuclei. Brain Res.101, 355–361 (1976)Google Scholar
  13. Kuruma, I., Bartholini, G., Tissot, R., Pletscher, A.: Comparative investigation of inhibition of extracerebral dopa decarboxylase in man and rats. J. Pharm. Pharmacol.24, 289–294 (1972)Google Scholar
  14. Lin, M. T.: Brain monoamines and temperature regulation. Ph. D. Thesis, Yale University (1977)Google Scholar
  15. Lin, M. T.: Effects of specific inhibitors of 5-hydroxytryptamine uptake on thermoregulation in rats. J. Physiol. (Lond.) (in press, 1978)Google Scholar
  16. Lin, M. T., Stitt, J. T.: Effects of brain monoamine depletion on the thermoregulatory responses of rabbits to different ambient temperatures. Physiologist19, 271 (1976)Google Scholar
  17. Lin, M. T., Pang, I. H., Chern, S. I., Chia W. Y.: Changes in serotonin contents in brain affects the metabolic heat production in the cold. Am. J. Physiol.235, R41-R47 (1978)Google Scholar
  18. Lin, M. T., Pang, I. H., Chern, Y. F., Chern, S. I.: Effects of 5,7-dihydroxytryptamine andp-chlorophenylalanine on temperature regulation in rats. J. Pharm Pharmacol. (in press, 1978b)Google Scholar
  19. Myers, R. D.: Impairment of thermoregulation, food and water intake in the after hypothalamic injections of 5,6-dihydroxytryptamine. Brain Res.94, 491–506 (1975)Google Scholar
  20. Myers, R. D., Yaksh, T. L.: Feeding and temperature responses in the unrestrained rat after injections of cholinergic and aminergic substances into the cerebral ventricles. Physiol. Behav.3, 917–928 (1968)Google Scholar
  21. Stitt, J. T.: Prostaglandin E1 fever induced in rabbits. J. Physiol. (Lond.)232, 163–179 (1973)Google Scholar
  22. Waller, M. B., Myers, R. D., martin, G. E.: Thermoregulatory deficits in the monkey produced by 5,6-dihydroxytryptamine injected into the hypothalamus. Neuropharmacology15, 61–68 (1976)Google Scholar
  23. Williams, A., Moberg, G. P.: Biogenic amines and acute thermal stress in the rat. Comp. Biochem. Physiol.51C, 67–71 (1975)Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • M. T. Lin
    • 1
  • C. F. Chow
    • 2
  • Y. F. Chern
    • 1
  • K. M. Wu
    • 1
  1. 1.Department of Physiology and BiophysicsNational Defense Medical CenterTaipeiTaiwan, Republic of China
  2. 2.Department of BiochemistryNational Defense Medical CenterTaipeiTaiwan, Republic of China

Personalised recommendations