, Volume 103, Issue 1, pp 28–32 | Cite as

Awakening properties of modafinil: effect on nocturnal activity in monkeys(Macaca mulatta) after acute and repeated administration

  • Jean-François Hermant
  • Francis A. Rambert
  • Jacques Duteil
Original Investigations


Single oral administration of modafinil (16–64 mg/kg) in monkeys induced an increase in nocturnal activity and in behavioural arousal without stereotyped behaviour. Modafinil-induced increase in nocturnal activity was prevented by the centrally acting α1 adrenoceptor antagonist prazosin. After repeated oral administration of modafinil, b.i.d. for 5 days, nocturnal activity was still increased, but was lower than after a single administration; the gradual decrease appeared on the second night. No rebound of sleep and no residual effect on night 5 (when modafinil was administered for 4 days and placebo on day 5) were seen after the withdrawal of the drug. Therefore, modafinil appeared to produce strong behavioural stimulation and awakening in a non-human primate species, after single, as well as after repeated administration, without other obvious side-effects (no sign of anxiety, no behavioural trouble). These awakening properties involved a modulation (stimulation) of a central α1 adrenergic system.

Key words

Modafinil Prazosin Awakening α1-Adrenoceptor Nocturnal activity Rhesus monkey 


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  1. Adams PM, Barratt ES (1974) Nocturnal sleep in squirrel monkeys. Electroencephalogr Clin Neurophysiol 36:201–204Google Scholar
  2. Alexander M, Isaac W (1965) Effect of illumination andd-amphetamine on the activity of the rhesus macaque. Psychol Rep 16:311–313Google Scholar
  3. Anden N-E, Strömbom U (1974) Adrenergic blocking agents: effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia 38:91–103Google Scholar
  4. Bastuji H, Jouvet M (1988) Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 12:695–700Google Scholar
  5. Billiard M, Picard E, Besset A, Maurel A (1987) Treatment of narcolepsy-cataplexy with modafinil, an alpha1-adrenoceptor agonist. Communication at the 5th International Congress of Sleep Research, Copenhagen, book of abstracts, p 471Google Scholar
  6. Davis GD (1957) Effects of central excitant and depressant drugs on locomotor activity in the monkey. Am J Physiol 188:619–623Google Scholar
  7. De Sarro GB, Asciotto C, Froio F, Libri V, Nistico G (1987) Evidence that the locus coeruleus is the site where clonidine and drugs acting at α1- and α2-adrenoceptors affect sleep and arousal mechanisms. Br J Pharmacol 90:675–685Google Scholar
  8. Dickinson SL, Gadie B, Tulloch IF (1988) α1-and α2-adrenoceptor antagonists differentially influence locomotor and stereotyped behaviour induced byd-amphetamine and apomorphine in the rat. Psychopharmacology 96:521–527Google Scholar
  9. Duteil J, Rambert FA, Pessonnier J, Gombert R, Assous E (1979) A possible α-adrenergic mechanism for drug (CRL40028)-induced hyperactivity. Eur J Pharmacol 59:121–123Google Scholar
  10. Duteil J, Rambert FA, Pessonnier J, Hermant JF, Gombert R, Assous E (1990) Central alpha1-adrenergic stimulation in relation to the behaviour stimulating effect of medafinil; studies with experimental animals. Eur J Pharmacol 180:49–58Google Scholar
  11. Fuxe K, Lidbrink P, Hökfelt T, Blome P, Goldstein M (1974) Effects of piperoxan on sleep and waking in the rat. Evidence for increased waking by blocking inhibitory adrenaline receptors on the locus coeruleus. Acta Physiol Scand 91:566–567Google Scholar
  12. Isaac W, Kallman MD (1979) Locomotor effects ofd-amphetamine and methylphenidate in young squirrel monkeys. Bull Psychon Soc 14:315–317Google Scholar
  13. Laffont F, Cathala HP, Kohler F (1987) Effect of modafinil on narcolepsy and idiopathic hypersomnia. Communication at the 5th International Congress of Sleep Research, Copenhagen, book of abstracts, p 536Google Scholar
  14. Lagarde D, Milhaud C (1989) Distinction between wakening and agitating effects of amphetamine in rhesus monkeys. Med Sci Res 17:961–963Google Scholar
  15. Lellouch J, Lazar Ph (1985) Méthodes statistiques en expérimentation biologique. Flammarion Médecine Sciences, ParisGoogle Scholar
  16. Lowther WR, Isaac W (1976) The effects ofd-amphetamine and illumination on behaviors of the squirrel monkey. Psychopharmacology 50:231–235Google Scholar
  17. Menkes DB, Baraban JM, Aghajanian GK (1981) Prazosin selectively antagonizes neuronal responses mediated by α1-adrenoceptors in brain. Naunyn Schmiedeberg's Arch Pharmacol 317:273–275Google Scholar
  18. Miczek KA, Gold LH (1983)d-Amphetamine in squirrel monkeys of different social status: effects on social and agonistic behaviour, locomotion and stereotypies. Psychopharmacology 81:183–190Google Scholar
  19. Milhaud CL, Klein MJ (1985) Effet de l'adrafinil sur l'activité nocturne du macaque rhésus(Macaca mulatta). J Pharmacol (Paris) 16:372–380Google Scholar
  20. Porsolt RD, Roux S, Jalfre M (1982) Antiapomorphine and locomotor effects of neuroleptics in rhesus monkeys. Pharmacol Biochem Behav 17:1309–1312Google Scholar
  21. Rambert FA, Pessonnier J, De Séréville JE, Pointeau AM, Duteil J (1986) Profil pharmacologique original de l'adrafinil chez la souris. J Pharmacol (Paris) 17:37–52Google Scholar
  22. Rambert FA, Moachon G, Multon MF, Matinier D, Pessonnier J, Clenet M, Duteil J (1987) Correlation of modafinil plasma levels to pharmacological activity in mice. Communication at the 5th International Congress of Sleep Research, Copenhagen, book of abstracts, p 124Google Scholar
  23. Randrup A, Munkvad I (1967) Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia 11:300–310Google Scholar
  24. Ridley RM, Baker HF (1982) Stereotypy in monkeys and human. Psychol Med 12:61–72Google Scholar
  25. Schwartz D (1981) Méthodes statistiques à l'usage des médecins et biologistes. Flammarion Médecine Sciences, ParisGoogle Scholar
  26. Scraggs PR, Ridley RM (1978) Behavioural effects of amphetamine in a small primate: relative potencies of thed- andl-isomers. Psychopharmacology 59:243–245Google Scholar
  27. Stinnette MJ Isaac W (1975) Behavioral effects ofd-amphetamine and caffeine in the squirrel monkey. Eur J Pharmacol 30:268–271Google Scholar
  28. Yellin AM, Hauty GT (1971) Activity cycles of the rhesus monkey(Macaca mulatta) under several experimental conditions, both in isolation and in a group situation. J Interdisciplinary Cycle Res 2:475–490Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Jean-François Hermant
    • 1
  • Francis A. Rambert
    • 1
  • Jacques Duteil
    • 1
  1. 1.Centre de Recherches du Laboratoire L. LafonMaisons-Alfort CedexFrance

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