Summary
The effect of clonidine (0.05 mg/kg i.p.) on 5-hydroxytryptamine (5-HT) turnover has been studied in the whole brain and in various cerebral areas of the rat (brain stem, hypothalamus, striatum and “rest” of the brain).
In the whole brain, clonidine produced a significant decrease (−23%) in 5-hydroxyindole acetic acid level and a slight increase (+7%) in 5-HT level. These variations were not observed in all the cerebral structures. The 5-hydroxyindole acetic acid levels were reduced in the hypothalamus and in the rest of the brain; they were not significantly altered in the brain stem and increased in the striatum.
The effect of clonidine on the 5-HT synthesis has been studied by evaluation of the rises in 5-HT levels induced by pargyline: these rises were found significantly increased in the brain stem and the hypothalamus and not significantly altered in the other cerebral structures.
These findings give support to the hypothesis according to which the norepinephrine receptor stimulation inhibits the activity in the 5-HT neurons: clonidine reduces primarily the release of 5-HT without an immediate effect on its synthesis. The differences observed among the various cerebral areas might be explained by the fact that relations between norepinephrine and 5-HT neurons do not exist identically in all cerebral structures.
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References
Andén, N.-E., Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurones to the telencephalon and diencephalon. Acta physiol. scand.67, 313–316 (1966).
Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci.9, 513–523 (1970).
Armijo, J. A., Florez, J.: The influence of increased brain 5-hydroxy-tryptamine upon the respiratory activity of cats. Neuropharmacol.13, 977–986 (1974).
Blondeaux, C., Juge, A., Sordet, F., Chouvet, G., Jouvet, M., Pujol, J. F.: Modification du métabolisme de la sérotonine (5-HT) cérébrale induite chez le Rat par administration de 6-hydroxydopamine. Brain Res.50, 101–114 (1973).
Boissier, J. R., Guidicelli, J. F., Fichelle, J., Schmitt, H., Schmitt, H.: Cardiovascular effects of 2-(2, 6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155). I. Peripheral sympathetic system. European J. Pharmacol.2, 333–339 (1968).
Bolme, P., Fuxe, K.: Pharmacological studies on a possible role of central noradrenaline neurons in respiratory control. J. Pharm. Pharmac.25, 351–352 (1973).
Bolme, P., Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Goldstein, M.: Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. European J. Pharmacol.28, 89–94 (1974).
Bralet, J., Rochette, L.: Effect of clonidine on the turnover rate of noradrenaline in peripheral tissues of the Rat. European J. Pharmacol.23, 239–244 (1973 a).
Bralet, J., Rochette, L.: Influence du traitement par la clonidine sur la synthèse des catécholamines dans le coeur, les glandes sous-maxillaires et la surrénale du Rat. Biochem. Pharmacol.22, 3173–3180 (1973 b).
Carlsson, A. H., Corrodi, H., Waldeck, B.: Substituierte Dopacetamide als Hemmer der Catechol-O-methyl-Transferase und der enzymatischen Hydroxylierung aromatischer Aminosäuren. In den Catecholamin-Metabolismus eingreifende Substanzen. 2. Helv. Chim. Acta46, 2270–2285 (1963).
Curzon, G., Green, A. R.: Rapid method for determination of 5-hydroxy-tryptamine and 5-hydroxyindoleacetique acid in small regions of Rat brain. Brit. J. Pharmacol.39, 653–655 (1970).
Fuxe, K., Jonsson, G.: Further mapping of central 5-hydroxytryptamine neurons: studies with the neurotoxic dihydroxytryptamines. In: Advances in Biochemical Psychopharmacol. (Costa, E., Gessa, G. L., Sandler, M., eds.), 10, pp. 1–12. New York: Raven Press. 1974.
Ito, A., Schanberg, S. M.: Maintenance of tonic vasomotor activity by alpha and beta adrenergic mechanisms in medullary cardiovascular centers. J. Pharmacol. Exp. Ther.189, 392–404 (1974).
Johnson, G. A., Kim, E. G., Boukma, S. J.: 5-hydroxyindole levels in Rat brain after inhibition of dopamineβ-hydroxylase. J. Pharmacol. Exp. Ther.180, 539–546 (1972).
Johnson, G. A., Kim, E. G.: Increase of brain levels of tryptophan induced by inhibition of dopamineβ-hydroxylase. J. Neurochem.20, 1761–1764 (1973).
Lloyd, K. G., Bartholini, G.: The effect of methiothepin on cerebral monoamine neurons. In: Advances in Biochemical Psychopharmacol. (Costa, E., Gessa, G. L., Sandler, M., eds.), 10, pp. 305–310. New York: Raven Press. 1974.
Maj, J., Baran, L., Grabowska, M., Sowinska, H.: Effect of clonidine on the 5-hydroxytryptamine and 5-hydroxyindoleacetic acid brain levels. Biochemical Pharmacol.22, 2679–2683 (1973).
Neumayr, R. J., Hare, D. H., Franz, D. N.: Evidence for bulbospinal control of sympathetic preganglionic neurons by monoaminergic pathways. Life Sci.14, 793–806 (1974).
Olson, L., Fuxe, K.: On the projections from the locus coeruleus noradrenaline neurons: the cerebellar innervation. Brain Res.28, 165–171 (1971).
Rochette, L., Bralet, A. M., Bralet, J.: Influence de la clonidine sur la synthèse et la libération de la noradrénaline dans différentes structures cérébrales du Rat. J. Pharmacol. (Paris)5, 2, 209–220 (1974).
Rochette, L., Bralet, J.: Effect of clonidine on the synthesis of cerebral dopamine. Biochem. Pharmacol.24, 303–305 (1975).
Scheel-Krüger, J., Hasselager, E.: Studies of various amphetamines, apomorphine and clonidine on body temperature and brain 5-hydroxytryptamine metabolism in Rats. Psychopharmacol.36, 189–202 (1974).
Schmitt, H., Schmitt, H., Boissier, J. R., Guidicelli, J. F., Fichelle, J.: Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline (St 155).II. Central sympathetic structure. European J. Pharmacol.2, 340–346 (1968).
Schmitt, H., Schmitt, H.: Localization of the hypotensive effect of 2-(2, 6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155, Catapresan). European J. Pharmacol.6, 8–12 (1969).
Schmitt, H., Schmitt, H., Fenard, S.: Evidence for a sympathomimetic component in the effects of Catapresan on vasomotor centres; antagonism by piperoxane. European J. Pharmacol.14, 98–100 (1971).
Starke, K., Wagner, J., Schümann, H. J.: Adrenergic neuron blockade by clonidine: comparison with guanethidine and local anesthetics. Arch. Intern. Pharmacodyn.195, 291–308 (1972).
Tsoucaris-Kupfer, D., Schmitt, H.: Hypothermic effect ofα-sympathomimetic agents and their antagonism by adrenergic and cholinergic blocking drugs. Neuropharmacol.11, 625–635 (1972).
Von Voigtlander, P. F., Moore, K. E.: Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum; effects of apomorphine, L-Dopa, amantadine, amphetamine and other psychomotor stimulants. Neuropharmacol.12, 451–462 (1973).
Wing, L. M. H., Chalmers, J. P.: Participation of central, serotoninergic neurons in the control of the circulation of the unanesthetized rabbit. Circ. Res.35, 504–513 (1974).
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Rochette, L., Bralet, J. Effect of the norepinephrine receptor stimulating agent “clonidine” on the turnover of 5-hydroxytryptamine in some areas of the rat brain. J. Neural Transmission 37, 259–267 (1975). https://doi.org/10.1007/BF01258653
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DOI: https://doi.org/10.1007/BF01258653