Summary
Male and female rats were compared with respect to brain serotonin (5-HT) levels, synthetic capacity, receptor sensitivity, and CNS functions. Levels of whole brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were higher in females. The accumulation of 5-HT after treatment with the monoamine oxidase inhibitor pargyline alone and in combination with the 5-HT precursor L-tryptophan was greater in females than in males. 5-HT increased and 5-HIAA decreased to the same extent in both sexes after administration of the 5-HT agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The temperature fall after all drug treatments was greater in females, but the “5-HT behavioural syndrome” was more pronounced in females merely after pargyline plus tryptophan; the behavioural response after 8-OH-DPAT did not differ between the sexes. These results are indicative of sex differences in the brain 5-HT neuronal systems. They are discussed in relation to differences between males and females in sexual behaviour, aggression and affective disorders.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahlenius, S., Larsson, K., Svensson, L.: Further evidence for an inhibitory role of central 5-HT in male rat sexual behaviour. Psychopharmacology68, 217–220 (1980).
Angst, J.: Genetic aspects of depression. In: Factors in Depression (Kline, N. S., ed.), pp. 1–19. New York: Raven Press. 1974.
Arvidsson, L.-E., Hacksell, U., Nilsson, J. L. G., Hjorth, S., Carlsson, A., Lindberg, P., Sanchez, D., Wikström, H.: 8-hydroxy-2-(di-n-propylamino)-tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist. J. Med. Chem.24, 921–923 (1981).
Åsberg, M., Bertilsson, L., Tuck, D., Cronholm, B., Sjöquist, F.: Indoleamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline. Clin. Pharmacol. Ther.14, 277–286 (1973).
Åsberg, M., Bertilsson, L., Mårtensson, B.: CSF monoamine metabolites, depression, and suicide. Adv. Biochem. Psychopharmacol.39, 87–97 (1984).
Biegon, A., Segal, M., Samuel, D.: Sex differences in behavioral and thermal responses to pargyline and tryptophan. Psychopharmacology61, 77–80 (1979).
Colton, T.: In: Statistics in medicine. Boston: Little, Brown. 1974.
Engel, J., Ahlenius, S., Almgren, O., Carlsson, A., Larsson, K., Södersten, P.: Effects of gonadectomy and hormone replacement on brain monoamine synthesis in male rats. Pharmacol. Biochem. Behavior10, 149–154 (1978).
Fischette, C. T., Biegon, A., McEwen, B. S.: Sex differences in serotonin 1 receptor binding in rat brain. Science222, 333–335 (1983).
Fischette, C. T., Biegon, A., McEwen, B. S.: Sex steroid modulation of the serotonin behavioral syndrome. Life Sci.35, 1197–1206 (1984).
Gozlan, H., El Mestikawy, S., Pichat, L., Glowinski, J., Hamon, M.: Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature305, 140–142 (1983).
Grahame-Smith, D. G.: Studiesin vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J. Neurochem.18, 1053–1066 (1971).
Hamon, M., Bourgoin, S., Gozlan, H., Hall, M. D., Goetz, C., Artaud, F., Horn, A. S.: Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain. Eur. J. Pharmacol.100, 263–276 (1984).
Hjorth, S.: Hypothermia in the rat induced by the potent serotonergic agent 8-OH-DPAT. J. Neural Transm.61, 131–135 (1985).
Hjorth, S., Carlsson, A., Lindberg, P., Sanchez, D., Wikström, H., Arvidsson, L. E., Hacksell, U., Nilsson, J. L. G.: 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT receptor stimulating activity. J. Neural Transm.55, 169–188 (1982).
Hyyppä, M., Rinne, U. K.: Hypothalamic monoamines after the neonatal androgenization, castration or reserpine treatment of the rat. Acta Endocrinol.66, 317–324 (1971).
Jacobs, B. L.: An animal behavior model for studying central serotonergic synapses. Life Sci.9, 777–786 (1976).
Kato, R.: Serotonin content of rat brain in relation to sex and age. J. Neurochem.5, 202 (1960).
Kueng, W., Wirz-Justice, A., Menzi, R., Chappuis-Arndt, E.: Regional brain variations of tryptophan, monoamines, monoamine oxidase activity, plasma free and total tryptophan during the estrous cycle of the rat. Neuroendocrinology21, 289–296 (1976).
Lucki, I., Frazer, A.: Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants. Psychopharmacology77, 205–211 (1982).
Marcinkiewicz, M., Vergé, D., Gozlan, H., Pichat, L., Hamon, M.: Autoradiographic evidence for the heterogeneity of 5-HT1 sites in the rat brain. Brain Res.291, 159–163 (1984).
Masur, J., Boerngen, R., Tufik, S.: Sex differences in the response to apomorphine in rats. Pharmacology20, 160–165 (1980).
Meyerson, B. J., Carrer, H., Eliasson, M.: 5-hydroxytryptamine and sexual behaviour in the female rat. Adv. Biochem. Psychopharmacol.11, 229–242 (1974).
Middlemiss, D. N.: 8-hydroxy-2-(di-n-propylamino)tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the (3H)5-HT recognition site. Arch. Pharmacol.327, 18–22 (1984).
Middlemiss, D. N., Fozard, J. R.: 8-hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur. J. Pharmacol.90, 151–153 (1983).
de Montigny, C., Blier, P., Chaput, Y.: Electrophysiologically identified serotonin receptors in the rat CNS. Neuropharmacol.23, 1511–1520 (1984).
Munaro, N. I.: The effect of ovarian steroids on hypothalamic 5-hydroxytryptamine neuronal activity. Neuroendocrinology26, 270–276 (1978).
Neff, N. H., Tozer, T. N.:In vivo measurement of brain serotonin turnover. Adv. Pharmacol.6 A, 97–109 (1968).
Peroutka, S. J., Lebovitz, R. M., Snyder, S. H.: Two distinct central serotonin receptors with different physiological functions. Science212, 827–829 (1981).
Rosecrans, J. A.: Differences in brain area 5-hydroxytryptamine turnover and rearing behavior in rats and mice of both sexes. Eur. J. Pharmacol.9, 379–382 (1970).
Rosecrans, J. A., Schechter, M. D.: Brain 5-hydroxytryptamine correlates of behaviour in rats: strain and sex variability. Physiol. Behav.8, 503–510 (1972).
Simon, N., Volicer, L.: Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. J. Neurochem.26, 893–900 (1976).
Sjöström, R., Roos, B.-E.: 5-hydroxyindolacetic acid and homovanillic acid in cerebrospinal fluid in manic-depressive psychosis. Eur. J. Clin. Pharmacol.4, 170–176 (1972).
Skillen, R. G., Thienes, C. H., Strain, L.: Brain 5-hydroxytryptamine, 5-hydroxytryptophan decarboxylase, and monoamine oxidase of normal, thyroidfed, and propylthiouracil-fed male and female rats. Endocrinology69, 1099–1102 (1961).
Vaccari, A., Brotman, S., Cimino, J., Timiras, P. S.: Sex differentiation of neurotransmitter enzymes in central and peripheral nervous systems. Brain Res.132, 176–185 (1977).
Valzelli, L.: 5-hydroxytryptamine in aggressiveness. Adv. Biochem. Psychopharmacol.11, 255–263 (1974).
Watts, A. G., Stanley, H. F.: Indoleamines in the hypothalamus and area of the midbrain raphe nuclei of male and female rats throughout postnatal development. Neuroendocrinology38, 461–466 (1984).
Winer, B. J.: In: Statistical principles in experimental design. New York-San Francisco-Toronto-London: McGraw-Hill. 1962.
Wirz-Justice, A., Chappuis-Arndt, E.: Sex specific differences in chlorimipramine inhibition of serotonin uptake in human platelets. Eur. J. Pharmacol.40, 21–25 (1976).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carlsson, M., Svensson, K., Eriksson, E. et al. Rat brain serotonin: Biochemical and functional evidence for a sex difference. J. Neural Transmission 63, 297–313 (1985). https://doi.org/10.1007/BF01252033
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01252033