Summary
In the rat, the insomnia which follows the administration of parachlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, is transiently reversed either by intra-cisternal injection of L-5-HTP or by an associated injection of 5-HTP and an L-aromatic-aciddecarboxylase inhibitor (benserazide). Histochemical, immunohistochemical and chemical investigations showed that 5-HTP administration does not lead to a detectable increase in cerebral 5-HT. These findings suggest that the restoration of sleep after p-CPA treatment could be mediated by the central action of 5-HTP.
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References
Aghajanian GK, Kuhar MJ, Roth RH (1973) Serotonin containing perikarya and terminals: differential effect of p-chlorophenylanine. Brain Res 54:85–101
Araneda S (1983) Contribution à l'étude du transport rétrograde de la sérotonine tritiée (3H-5HT) Thèse d'Etat. LYON
Bartholini G, Pletscher A (1968) Cerebral accumulation and metabolism of C14-DOPA after selective inhibition of peripheral decarboxylase. J Pharmacol Exp Ther 161:14–20
Bronzino J, Stern J, Leahy P, Morgane P (1976) Sleep cycles in cats during chronic electrical stimulation of the area postrema and the anterior raphe. Brain Res Bull 1:235–239
Carlsson A, Lindqvist M (1973) In-vivo measurements of tryptophan and tyrosine hydroxylase activities in mouse brain. J Neural Transm 34:79–91
Cespuglio R, Sarda N, Gharib A, Chastrette N, Houdouin F, Rampin C, Jouvet M (1990) Voltammetric detection of the release of 5-hydroxyindole compounds throughout the sleep waking cycle of the rat. Exp Brain Res 80:121–128
Coindet J, Chouvet G, Mouret J (1975) Effect of lesions of the suprachiasmatic nuclei on paradoxical sleep and slow wave sleep circadian rhythms in the rat. Neurosci Lett 1:243–247
Denoyer M, Sallanon M, Kitahama K, Aubert C, Jouvet M (1989) Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5 hydroxytryptophan. Neuroscience 28:83–94
Florio V, Scotti de Carolis A, Longo VG (1968) Observations on the effect of DL-Parachlorophenylalanine on the electroencephalogram. Physiol Behav 3:861–863
Geffard M, Dulluc J, Rock AM (1985) Antisera against the indolkylamines: tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-methoxytryptophan and 5-methoxytryptamine tested by an enzyme-linked immunosorbent assay method. J Neurochem 44:1221–1228
Geffard M, Touret M, Kitahama K (1987) First characterization of 5-hydroxytryptophan in rat brain by using specific antibodies. Brain Res 426:191–196
Gharib A, Reynaud D, Sarda N, Vivien-Roels B, Pevet P, Pacheco H (1989) Adenosine analogs elevate N-acetylserotonin and melatonin in rat pineal gland. Neurosci Lett 106:345–349
Jung MJ, Palfreyman MG, Wagner J, Bey P, Ribereau-Gayon, Zraika M, Koch-Weser (1979) Inhibition of monoamine synthesis by irreversible blockade of aromatic aminoacid decarboxylase with α-monofluoromethyldopa. Life Sci 24:1037–1042
Koella WP, Czicman J (1966) Mechanism of the EEG synchronising action of serotonin. Am J Physiol 4:926–934
Kollonitsch J, Patchett A, Marburg S, Maycock AL, Perkins LM, Doldodouras GA, Duggan DE, Aster SD (1978) Selective inhibitors of biosynthesis of aminergic neurotransmitters. Nature 274:906–908
Kuhar M, Yamamura HI (1976) Localization of cholinergic muscarinic receptors in rat brain by light microscopic radioautography. Brain Res 110:229–243
Laguzzi R, Adrien J (1980) Inversion de l'insomnie produite par la p-chlorophenylalanine chez le rat: administration intrapéritoneale et intraventriculaire de 5-hydroxytryptophane. Arch Ital Biol 118:109–123
Louis-Coindet J, Sarda N, Pacheco H, Jouvet M (1984) Effect of S-Adenosyl-L-Homocysteine upon sleep in p-Chlorophenylalanine pretreated rats. Brain Res 294:239–245
Marks GA, Roffwarg HP (1988) PGO waves and insomnia in p-CPA-treated rats. Pharm Biochem Behav 31:509–513
Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–450
Petitjean F, Touret M, Buda C, Salvert D, Jouvet M, Bobillier P (1981) Selective identification of indole amine containing neurons under particular pharmacological (p-CPA, 5-HTP) and behavioral situations (sleep). J Physiol (Paris) 77:237–240
Petitjean F, Buda C, Sallanon M, Jouvet M (1985) Insomnie par administration de parachlorophenylalanine: réversibilité par injection périphérique ou centrale de 5-hydroxytryptophane et de sérotonine. Sleep 8:56–67
Pletscher A, Gey KF (1963) The effect of a new decarboxylase inhibitor on endogenous and exogenous monoamines. Biochem Pharmacol 12:223–228
Rechtschaffen A, Lovell RA, Freedman DX, Hitehead WE, Aldrich M (1973) Serotonin and behavior. Academic Press, New York London, p 401
Riou F, Cespuglio R, Jouvet M (1982) Endogenous peptides and sleep in the rat: III the hypnogenic properties of vasoactive intestinal polypeptide. Neuropeptides 2:265–278
Ritzen M, Hammarström L, Ullberg S (1969) Autoradiographic distribution of 5-hydroxytryptamine and 5-hydroxytryptophan in the mouse. Biochem Pharmacol 14:313–321
Roth GI, Walton PJ, Yamamoto WS (1970) Area postrema: abrupt EEG synchronization following close intra-arterial perfusion with serotonin. Brain Res 23:223–233
Sakumoto T, Sakai K, Jouvet M, Kimura H, Maeda T (1984) 5-HT immunoreactive hypothalamic neurons in rat and cat after 5-HTP administration. Brain Res Bull 12:721–733
Sakurada T, Kisara K (1977) Effects of P-chlorophenylalanine (P-CPA) on sleep in olfactory bulb lesioned rats. Jpn J Pharmacol 27:389–395
Sallanon M, Petitjean F, Buda C, Janin M, Jouvet M (1983) Mise en jeu de structures hypothalamiques dans les mécanismes indolaminergiques du sommeil paradoxal. CR Acad Sci (Paris) 297
Sallanon M, Kitahama K, Denoyer M, Gay N, Jouvet M (1986) Insomnie de longue durée après lésions des pérykarions de l'aire préoptique paramédiane chez le chat. CR Acad Sci (Paris) 303
Sarna GS, Hutson PS, Tricklebank Curzon G (1983) Determination of brain 5-hydroxytryptamine turnover in freely moving rats using repeated sampling of cerebrospinal fluid. J Neurochem 40:383–388
Steigrad P, Tobler I, Waser PG, Borbely AA (1978) Effect of p-Chlorophenylalanine on cerebral serotonin binding, serotonin concentration and motor activity in the rat. Naun Schmied Arch Pharmacol 305:143–148
Tobler I, Borbely AA (1982) Sleep regulation after reduction of brain serotonin: Effect of p-parachlorophenylalanine combined with sleep deprivation in the rat. Sleep 5:145–153
Touret M, Pasqualini C, Bobillier P, Kerdelhue B, Jouvet M (1984) Sites de liaison pour le 5-hydroxytryptophane dans le noyau oculomoteur et le noyau rouge du cerveau de rat. CR Acad Sci (Paris) 299:427–430
Touret M, Kitahama K, Geffard M, Jouvet M (1987) 5-hydroxytryptophan (5-HTP)-immunoreactive neurons in the rat brain tissue. Neurosci Lett 80:263–267
Vanderwolf CH (1988) Cerebral activity and behavior: control by central cholinergic and serotoninergic systems. Int Rev Neurobiol 30:225–340
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Touret, M., Sarda, N., Gharib, A. et al. The role of 5-hydroxytryptophan (5-HTP) in the regulation of the sleep/wake cycle in parachlorophenylalanine (p-CPA) pretreated rat: a multiple approach study. Exp Brain Res 86, 117–124 (1991). https://doi.org/10.1007/BF00231046
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DOI: https://doi.org/10.1007/BF00231046