Summary
The acute effects of reserpine on the sleep-wakefulness cycle were systematically studied in five male rabbits with chronically implanted electrodes for recording the EEG, the EMG of the neck muscles, and the oculogram. After careful control studies during which the rabbits became accustomed to the experimental situation and attained stable sleep-wakefulness patterns, various doses of reserpine (1.0, 0.5, 0.25, 0.1, 0.05 mg/kg) were injected intravenously and 5-hr polygraphic recordings were made. Twenty-four hours after administration, 2-hr recordings were made for all doses studied; for the dose of 1.0 mg/kg 2-hr recordings were also made 48 hours after administration.
The percent times of the three stages, alert, slow wave sleep and paradoxical sleep, were calculated for the total recording time. In the unmedicated animals the percentages during 2-hr recordings were: alert, 32.9±5.7; slow wave sleep, 61.5±5.9; and paradoxical sleep, 5.6±1.1. Paradoxical sleep was also calculated for the first hour and the remaining 4 hours of the 5-hr recording period both as to percent time and the duration of single episodes. Some behavioral and polygraphic characteristics of paradoxical sleep were described.
Reserpine, in doses of 1.0 to 0.25 mg/kg, caused a biphasic response; an initial alert period of 1 1/2 to 2 hours followed by a slow-wave-sleep period which endured until the end of the 5-hr recording. Suppression of paradoxical sleep was observed with doses of 1.0 to 0.1 mg/kg, although the doses of 0.25 and 0.1 mg/kg did not suppress it during the first hour after injection. The percent time of paradoxical sleep in total recording time showed a dose-dependent decrease: 0.2% for 1.0 mg/kg, 0.1% for 0.5 mg/kg, (both significant,p<0.001), 0.6% for 0.25 mg/kg (p<0.01), 2.4% for 0.1 mg/kg (p<0.05), 3.5% for 0.05 mg/kg (not significant) and 5.1% for the saline control. The duration of single episodes of paradoxical sleep was not changed by reserpine. In the 2-hr recordings made one and two days after reserpine administration the percent time of paradoxical sleep did not differ significantly from the normal level.
Similar content being viewed by others
References
Brooks, D. C., Bizzi, E.: Brain stem electrical activity during deep sleep. Arch. ital. Biol.101, 648–665 (1963).
Carlsson, A., Rosengren, E., Bertler, A., Nilsson, J.: Effect of reserpine on the metabolism of catechol amines. In: Psychotropic Drugs (S. Garattini and V. Ghetti, Eds.), pp. 363–372. Amsterdam: Elsevier 1957.
Delorme, F., Jeannerod, M., Jouvet, M.: Effets remarquables de la réserpine sur l'activité EEG phasique ponto-géniculo-occipitale. C. R. Soc. Biol. (Paris)159, 900–903 (1965).
Faure, J.: Le sommeil “paradoxal” du lapin dans ses aspects anatomofonctionnels et hormonaux. In: Neurophysiologie des États de Sommeil, M. Jouvet (Ed.), pp. 241–283. Paris: Centre National de la Recherche Scientifique 1965.
Gonnard, P., Nechtschein, S., Schmitt, H.: Action de la réserpine sur l'electroencéphalogramme du lapin. Arch. int. Pharmacodyn.110, 265–274 (1957).
Gottesmann, C.: Réserpine et vigilance chez le rat. C. R. Soc. Biol. (Paris)160, 2056–2061 (1966).
Hartmann, E. L.: Reserpine: Its effect on the sleep-dream cycle in man. Psychopharmacologia (Berl.)9, 242–247 (1966).
Jeannerod, M.: Organisation de l'activité électrique phasique du sommeil paradoxal. Lyon: L.M.D. 1965.
Jouvet, M.: Neurophysiology of the state of sleep. Physiol. Rev.47, 117–177 (1967).
—: Biogenic amines and the state of sleep. Science163, 32–41 (1969).
Kawakami, M., Sawyer, C. H.: Induction of behavioral and electroencephalographic changes in the rabbit by hormone administration or brain stimulation. Endocrinology65, 631–643 (1959).
Khazan, N., Kawakami, M., Sawyer, C. H.: Physiological and pharmacological aspects of paradoxical sleep in the rabbit. Pharmacologist5, 266 (1963).
—: Mechanisms of paradoxical sleep as revealed by neurophysiologic and pharmacologic approaches in the rabbit. Psychopharmacologia (Berl.)5, 457–466 (1964).
Longo, V. G., Napolitano, L.: Effeti della reserpina sulle reazioni elettroencefalographiche e motorie provocate della stimolazione dell'ipotalamo. Farmaco, Il (Pavia), Ed. Sci.10, 297–305 (1955).
Matsumoto, J., Jouvet, M.: Effets de réserpine, DOPA et 5-HTP sur les deux états de sommeil. C. R. Soc. Biol. (Paris)158, 2137–2140 (1964).
Monnier, M., Gangloff, H.: Atlas for stereotaxic brain research on the conscious rabbit, Rabbit Brain Research, Vol. 1. Amsterdam: Elsevier 1961.
Pirch, J. H., Rech, R. H., Moore, K. E.: Depression and recovery of the electrocorticogram, behavior and brain amines in rats treated with reserpine. Int. J. Neuropharmacol.6, 375–385 (1967).
Pletscher, A., Shore, P. A., Brodie, B. B.: Serotonin release as a possible mechanism of reserpine action. Science122, 374–375 (1955).
Pscheidt, G. R., Steiner, W. G., Himwich, H. E.: An electroencephalographic and chemical re-evaluation of the central action of reserpine in the rabbit. J. Pharmacol. exp. Ther.144, 37–44 (1964).
Sawyer, C. H., Kawakami, M.: Characteristics of behavioral and electroencephalographic after-reactions to copulation and vaginal stimulation in the female rabbit. Endocrinology65, 622–630 (1959).
Sterman, M. B., Knauss, T., Lehmann, D., Clemente, C. D.: Circadian sleep and waking patterns in the laboratory cat. Electroenceph. clin. Neurophysiol.19, 509–517 (1965).
Tissot, R.: The effect of certain drugs on the sleep cycle in man. In: Progress in Brain Research, Sleep Mechanisms (K. Akert, C. Bally, and J. P. Schadé, Eds.), Vol. 18, pp. 175–177. Amsterdam: Elsevier 1965.
Williams, R. L., Agnew, H. W., Jr., Webb, W. B.: Sleep patterns in young adults: An EEG study. Electroenceph. clin. Neurophysiol.17, 376–381 (1964).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tabushi, K., Himwich, H.E. The acute effects of reserpine on the sleep-wakefulness cycle in rabbits. Psychopharmacologia 16, 240–252 (1969). https://doi.org/10.1007/BF02456048
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02456048