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The stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice

A comparison with dexamphetamine


Modafinil is a new drug used in the treatment of narcolepsy. Its administration in mice induced a dose-dependent increase in locomotor activity. The effects of modafinil were compared with those of dexamphetamine on three tests that assessed the anxiety level (drugs were used at doses which induced a roughly similar stimulation of locomotor activity). Dexamphetamine increased the latency of exploration of a white compartment, increased thigmotaxis in an open-field and decreased the time spent in the open arms of an elevated plus-maze. None of these responses was significantly modified by modafinil. We conclude that modafinil does not share the anxiogenic effects of dexamphetamine.

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  • Bastuji H, Jouvet M (1988) Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 12:695–700

    Google Scholar 

  • Billiard M, Picard E, Besset A, Mavrel A (1987) Treatment of narcolepsy cataplexy with modafinil, an alpha 1 adrenoreceptor agonist. Communication at the 5th International Congress of Sleep Research, Copenhagen 1987, Book of abstracts, p 471

  • Brookes LG (1985) Central nervous system stimulants. In: (Iversen SD) Psychopharmacology: recent advances and future prospects. British Association for Psychopharmacology monograph no. 6, Oxford Medical Publications, pp 264–277

  • Charney DS, Heninger GR, Jatlow PI (1985) Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry 42:233

    Google Scholar 

  • Chiueh C, Moore K (1974) Relative potencies ofd- andl- amphetamine in the release of dopamine from cat brain in vivo. Res Commun Chem Pathol Pharmacol 7:189–199

    Google Scholar 

  • Duteil J, De Sereville JE, Boer C, Rambert FA (1990a) Lack of dopaminergic involvement in modafinil, but not amphetamine and methylphenidate, activity in anaesthetized mice and rats: in vivo voltammetry study. Eur J Pharmacol 183 [4]:1406–1407

    Google Scholar 

  • Duteil J, Rambert F, Pessonnier J, Hermant JF, Gombert R, Assous E (1990b) Central alpha1 adrenergic stimulation in relation to the awakening activity of modafinil: behavioural studies in laboratory animals. Eur J Pharmacol 180:49–58

    Google Scholar 

  • Ferris R, Tang F, Maxwell R (1972) A comparison of the capacities of isomers of amphetamine, deoxypipradol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex, hypothalamus, striatum and adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther 181:407–417

    Google Scholar 

  • Freixanet MG (1978) Medidas conductuales en campo abierto. Rev Psicol Gen Appl 33:657–672

    Google Scholar 

  • Geller I, Seifter J (1960) The effects of meprobamate, barbiturates,d-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492

    Google Scholar 

  • Hermant J, Rambert F, Duteil J (1991) Awakening properties of modafinil: effect on nocturnal activity in monkeys (Macaca mulatta) after acute and repeated administration. Psychopharmacology: 103:28–32

    Google Scholar 

  • Lapin IP (1993) Anxiogenic effect of phenylethylamine and amphetamine in the elevated plus-maze in mice and its attenuation by ethanol. Pharmacol Biochem Behav 44:241–243

    Google Scholar 

  • Lin JS, Roussel B, Akaoka H, Fort P, Debilly G, Jouvet M (1992) Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat. Brain Res 591:319–326

    Google Scholar 

  • Lister GL (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185

    Google Scholar 

  • Pellow S, Chopin P, Briley M, File SE (1985) The validation of open: closed arm entries in an elevated plus-maze: a novel test of anxiety in the rat. J Neurosci Methods 14:149–167

    Google Scholar 

  • Rambert FA, Pessonnier J, Duteil J (1990) Modafinil, amphetamine and methylphenidate-induced hyperactivities in mice involve different mechanisms. Eur J Pharmacol 183 [2]:455–456

    Google Scholar 

  • Simon P, Panissaud C, Costentin J (1992) Sulpiride anxiogenic-like effect inhibition by a D1 dopamine receptor antagonist. Neuroreport 3:941–942

    Google Scholar 

  • Simon P, Panissaud C, Costentin J (1993) Anxiogenic effects induced by stimulation of dopamine receptors. Pharmacol Biochem Behav 45:685–690

    Google Scholar 

  • Simon P, Dupuis R, Costentin J (1994) Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res (in press)

  • Treit D, Fundytus M (1989) Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol Biochem Behav [31]:959–962

    Google Scholar 

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Simon, P., Panissaud, C. & Costentin, J. The stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice. Psychopharmacology 114, 597–600 (1994).

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Key words

  • Anxiety
  • Modafinil
  • Dexamphetamine
  • Black/white compartments
  • Elevated maze-plus
  • Thigmotaxis
  • Wakefulness