Summary
The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain. The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. A parallel change in the concentration of 5-hydroxytryptamine was seen in brain stem and striatal region of adrenalectomized rats. In contrast, the level of 5-hydroxyindoleacetic acid was significantly elevated in both of these brain regions. Replacement therapy with corticosterone (10 mg/kg i.p.) produced time-dependent increases in tryptophan, tryptophan hydroxylase and 5-hydroxytryptamine and decreases in 5-hydroxyindoleacetic acid levels. Alterations in these neurochemical parameters were more conspicuous in adrenalectomized rats receiving corticosterone for 7 days as compared to those given only for 3 days. Our data demonstrate that adrenocortical hormones regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate-limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine.
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References
Azmitia, E. C., McEwen, B. S. Corticosterone regulation of tryptophan hydroxylase in mid-brain of the rat. Science166, 1274–1276 (1969).
Curzon, G., Green, A. R. Effect of hydrocortisone on rat brain 5-hydroxytryptamine. Life Sci.7, 657–663 (1968).
Curzon, G., Green, A. R. Effects of immobilization on rat liver tryptophan pyrrolase and brain 5-hydroxytryptamine metabolism. Brit. J. Pharmacol.37, 690–697 (1969).
Curzon, G., Green, A. R. Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in small regions of rat brain. Brit. J. Pharmacol.39, 653–655 (1970).
Dominic, J. A. In: Serotonin and Behaviour (Barchas, J., Usdin, E., eds.), pp. 149–155. New York: Academic Press. 1973.
Fuxe, K., Hökfelt, T., Ungerstedt, U. Localization of indolealkyl amines in CNS. In: Adv. Pharmacol. and Chemother. (Garattini, S., Shore, P. A., eds.), Vol. 6A, pp. 235–261. New York: Academic Press. 1968.
Gessa, G. L., Tagliamonte, A. In: Aromatic amino acids in the brain. Ciba Foundation Symposium, pp. 207–216. Elsevier/Excerpta Medica/North Holland. 1974.
Glowinski, J., Iversen, L. L. Regional studies of catecholamines in the rat brain. The disposition of (3H)norepinephrine, (3H)dopamine and (3H)DOPA in various regions of the brain. J. Neurochem.13, 655–669 (1966).
Hamon, M., Glowinski, J. Regulation of serotonin synthesis (Minireview). Life Sci.15, 1533–1548 (1974).
Hess, S. M., Udenfriend, S. A Fluorometric procedure for the measurement of tryptamine in tissues. J. Pharmacol. Exp. Ther.127, 175–177 (1959).
Jequier, E., Robinson, D. S., Lovenberg, W., Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brain stem and beef pineal. Biochem. Pharmacol.18, 1071–1081 (1969).
Knapp, S., Mandell, A. J. Short and long-term Lithium administration: Effects on the brains serotonergic biosynthetics systems. Science180, 645–647 (1973).
Korf, J., Van Praag, H. M., Sebens, J. B. Serum tryptophan decreased, brain tryptophan increased and brain serotonin synthesis unchanged after probenecid loading. Brain Res.42, 239–242 (1972).
Krieger, D. T., Rizzo, F. Serotonin mediation of circadian periodicity of plasma 17-hydroxycorticosteroids. Amer. J. Physiol.217, 1703–1707 (1969).
Lovenberg, W., Besselar, G. H., Bensinger, R. E., Jackson, R. L. Physiological and drug-induced regulation of Serotonin Synthesis. In: Serotonin and Behaviour (Barchas, J., Usdin, E., eds.), pp. 49–54. New York: Academic Press. 1973.
Macon, J. B., Sokoloff, L., Glowinski, J. Feedback control of rat brain 5-HT synthesis. J. Neurochem.18, 323–331 (1971).
Martini, L., Ganong, W. F. (eds.): Neuroendocrinology, Vol. 1, pp. 283 to 366. New York-London: Academic Press. 1966.
Martini, L., Molta, M., Fraschini, F. (eds.): The Hypothalamus, pp. 123 to 166. New York-London: Academic Press. 1970.
McKinney, W. T., Prange, A. J., jr., Majchovicz, F., Schlesinger, K. Plasma corticosterone changes following alterations in brain norepinephrine and serotonin. Dis. Nerv. Syst.32, 308–313 (1971).
Neckers, L., Sze, P. Y. Regulation of 5-hydroxytryptamine metabolism in mouse brain by adrenal glucocorticoids. Brain Res.93, 123–135 (1975).
Peters, D. A. V., McGeer, P. L., McGeer, E. G. The distribution of tryptophan hydroxylase in cat brain. J. Neurochem.15, 1431–1435 (1968).
Rastogi, R. B., Lapierre, Y. D., Singhal, R. L. Evidence for the role of brain biogenic amines in depressed motor activity seen in chemically thyroidectomized rats. J. Neurochem.26, 443–449 (1976).
Rastogi, R. B., Singhal, R. L. Thyroid hormone control of 5-hydroxy-tryptamine metabolism in developing brain. J. Pharmacol. Exp. Ther.191, 72–81 (1974).
Rastogi, R. B., Singhal, R. L. Lithium-modification of behavioural activity and brain biogenic amines in developing hyperthyroid rats. J. Pharmacol. Exp. Therap.201, 92–102 (1977).
Scapagnini, U., Moberg, G. F., Van Loon, G. R., DeGroof, J., Ganong, W. F. Relation of brain 5-hydroxytryptamine content to the diurnal variation in plasma corticosterone in the rat. Neuroendocrinology7, 90–96 (1971).
Selye, H. Perspectives in stress research. Perspect. Biol. Med.2, 403–413 (1959).
Shah, N. S., Stevens, S., Himwich, H. E. Effect of chronic administration of cortisone on the tryptophan induced changes in amine levels in the rat brain. Arch. Int. Pharmacodyn. Ther.171, 285–295 (1968).
Sze, P. Y., Neckers, L., Towle, A. C. Glucocorticoids as a regulatory factor for brain tryptophan hydroxylase. J. Neurochem.26, 169–173 (1976).
Takahashi, R., Aprison, M. H. Acetylcholine content of discrete areas of the brain obtained by a near-freezing method. J. Neurochem.11, 887–898 (1964).
Telegdy, G., Vermes, I. Effect of adrenocortical hormones on activity of the serotoninergic system in limbic structures in rats. Neuroendocrinology18, 16–26 (1975).
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Rastogi, R.B., Singhal, R.L. Adrenocorticoids control 5-hydroxytryptamine metabolism in rat brain. J. Neural Transmission 42, 63–71 (1978). https://doi.org/10.1007/BF01262730
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DOI: https://doi.org/10.1007/BF01262730