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Behavioral effects of modafinil in marmoset monkeys

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Abstract

Rationale

Modafinil is increasingly used in sleep disturbances in general and in neurodegenerative diseases and is recently being used in healthy people for attention control. However, the application of modafinil is possibly not only restricted to alertness enhancing effects. More insight in this compound may lead to new applications. Not all behavioral aspects have been studied sufficiently; therefore, more detailed investigations on modafinil’s positive and aversive behavioral effects are addressed in this paper.

Objectives

Determination of effects of modafinil in marmoset monkeys with observational methods and with behavioral tests measuring locomotor activity, hand–eye coordination, response to a threat situation and startle response.

Materials and methods

Two hours after oral administration of modafinil in doses of 50, 100, 150, and 225 mg/kg, animals were observed and tested in the behavioral test systems.

Results

Locomotor activity was increased after 100 mg/kg modafinil in the Bungalow test and after 100, 150, and 225 mg/kg, as found in the movement parameters of the human threat test. Moreover, modafinil showed anxiolytic-like effects in the human threat test. No other side effects were observed, nor were the hand–eye coordination and startle response affected.

Conclusions

Besides psychostimulation, modafinil has no aversive effects in the doses used in the domains measured. The potential anxiolytic-like effects of modafinil may create new possibilities for the therapeutic use of modafinil.

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References

  • Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J (2003) Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson’s disease. Mov Disord 18:287–293

    Article  PubMed  Google Scholar 

  • Anden NE, Strombom U, Svensson TH (1973) Dopamine and noradrenaline receptor stimulation: reversal of reserpine-induced suppression of motor activity. Psychopharmacologia 29:289–298

    Article  PubMed  CAS  Google Scholar 

  • Barros M, Tomaz C (2002) Non-human primate models for investigating fear and anxiety. Neurosci Biobehav Rev 26:187–201

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Beasley CM, Dellva MA, Tamura RN, Morgenstern H, Glazer WM, Ferguson K, Tollefson GD (1999) Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. Br J Psychiatry 174:23–30

    Article  PubMed  CAS  Google Scholar 

  • Carey GJ, Costall B, Domeney AM, Jones DN, Naylor RJ (1992) Behavioural effects of anxiogenic agents in the common marmoset. Pharmacol Biochem Behav 42:143–153

    Article  PubMed  CAS  Google Scholar 

  • Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ (1988) Zacopride: anxiolytic profile in rodent and primate models of anxiety. J Pharm Pharmacol 40:302–305

    PubMed  CAS  Google Scholar 

  • Di Monte DA, McCormack A, Petzinger G, Janson AM, Quik M, Langston WJ (2000) Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model. Mov Disord 15:459–466

    Article  PubMed  Google Scholar 

  • Duteil J, Rambert FA, Pessonnier J, Hermant JF, Gombert R, Assous E (1990) Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals. Eur J Pharmacol 180:49–58

    Article  PubMed  CAS  Google Scholar 

  • Eden RJ, Costall B, Domeney AM, Gerrard PA, Harvey CA, Kelly ME, Naylor RJ, Owen DA, Wright A (1991) Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav 38:147–154

    Article  PubMed  CAS  Google Scholar 

  • Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC (1998) Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine. Neuroscience 87:905–911

    Article  PubMed  CAS  Google Scholar 

  • Ferraro L, Tanganelli S, O’Connor WT, Antonelli T, Rambert F, Fuxe K (1996) The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor. Neurosci Lett 220:5–8

    Article  PubMed  CAS  Google Scholar 

  • Ferraro L, Antonelli T, O’Connor WT, Tanganelli S, Rambert FA, Fuxe K (1998) The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striato-pallidal GABA transmission. Neurosci Lett 253:135–138

    Article  PubMed  CAS  Google Scholar 

  • Ferraro L, Antonelli T, Tanganelli S, O’Connor WT, Perez de la Mora M, Mendez-Franco J, Rambert FA, Fuxe K (1999) The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade. Neuropsychopharmacology 20:346–356

    Article  PubMed  CAS  Google Scholar 

  • Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    PubMed  CAS  Google Scholar 

  • Green PM, Stillman MJ (1998) Narcolepsy. Signs, symptoms, differential diagnosis, and management. Arch Fam Med 7:472–478

    Article  PubMed  CAS  Google Scholar 

  • Guy W (1976) ECDEU assessment manual for psychopharmacology. U.S. Department of Health, Education and Welfare, Washington, District of Columbia, pp 534–537

    Google Scholar 

  • Happe S (2003) Excessive daytime sleepiness and sleep disturbances in patients with neurological diseases: epidemiology and management. Drugs 63:2725–2737

    Article  PubMed  Google Scholar 

  • Happe S, Pirker W, Sauter C, Klosch G, Zeitlhofer J (2001) Successful treatment of excessive daytime sleepiness in Parkinson’s disease with modafinil. J Neurol 248:632–634

    Article  PubMed  CAS  Google Scholar 

  • Jasinski DR, Kovacevic-Ristanovic R (2000) Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy. Clin Neuropharmacol 23:149–156

    Article  PubMed  CAS  Google Scholar 

  • Jenner P, Zeng BY, Smith LA, Pearce RK, Tel B, Chancharme L, Moachon G (2000) Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated common marmoset. Exp Brain Res 133:178–188

    Article  PubMed  CAS  Google Scholar 

  • Katzenschlager R, Manson AJ, Evans A, Watt H, Lees AJ (2004) Low dose quetiapine for drug induced dyskinesias in Parkinson’s disease: a double blind cross over study. J Neurol Neurosurg Psychiatry 75:295–297

    PubMed  CAS  Google Scholar 

  • Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128

    Article  PubMed  CAS  Google Scholar 

  • Larijani GE, Goldberg ME, Hojat M, Khaleghi B, Dunn JB, Marr AT (2004) Modafinil improves recovery after general anesthesia. Anesth Analg 98:976–981

    Article  PubMed  CAS  Google Scholar 

  • Lin JS, Hou Y, Jouvet M (1996) Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci U S A 93:14128–14133

    Article  PubMed  CAS  Google Scholar 

  • Makela EH, Miller K, Cutlip WD (2003) Three case reports of modafinil use in treating sedation induced by antipsychotic medications. J Clin Psychiatry 64:485–486

    Article  PubMed  Google Scholar 

  • Menza MA, Kaufman KR, Castellanos A (2000) Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry 61:378–381

    PubMed  CAS  Google Scholar 

  • Mignot E, Nishino S, Guilleminault C, Dement WC (1994) Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep 17:436–437

    PubMed  CAS  Google Scholar 

  • Nemeroff CB (2003) The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull 37:133–146

    PubMed  Google Scholar 

  • Nieves AV, Lang AE (2002) Treatment of excessive daytime sleepiness in patients with Parkinson’s disease with modafinil. Clin Neuropharmacol 25:111–114

    Article  PubMed  CAS  Google Scholar 

  • Ninan PT, Hassman HA, Glass SJ, McManus FC (2004) Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue. J Clin Psychiatry 65:414–420

    PubMed  CAS  Google Scholar 

  • Philippens IH, Melchers BP, Roeling TA, Bruijnzeel PL (2000) Behavioral test systems in marmoset monkeys. Behav Res Meth Instrum Comput 32:173–179

    CAS  Google Scholar 

  • Philippens IH, Kersten CJ, Vanwersch RA, Strijkstra AM (2004) Sleep and sleep EEG data in marmoset monkeys. Sleep wake research in the Netherlands, vol 15. NSWO, Leiden, The Netherlands, pp 49–51

    Google Scholar 

  • Rammohan KW, Rosenberg JH, Lynn DJ, Blumenfeld AM, Pollak CP, Nagaraja HN (2002) Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry 72:179–183

    Article  PubMed  CAS  Google Scholar 

  • Robertson P, Jr., Hellriegel ET (2003) Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet 42:123–137

    Article  PubMed  CAS  Google Scholar 

  • Scammell TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS, Saper CB (2000) Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 20:8620–8628

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Simon P, Hemet C, Ramassamy C, Costentin J (1995) Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice. Eur Neuropsychopharmacol 5:509–514

    Article  PubMed  CAS  Google Scholar 

  • Stevenson MF, Poole TB (1976) An ethogram of the common marmoset (Calithrix jacchus jacchus): general behavioural repertoire. Anim Behav 24:428–451

    Article  PubMed  CAS  Google Scholar 

  • Tanganelli S, Perez de la Mora M, Ferraro L, Mendez-Franco J, Beani L, Rambert FA, Fuxe K (1995) Modafinil and cortical gamma-aminobutyric acid outflow. Modulation by 5-hydroxytryptamine neurotoxins. Eur J Pharmacol 273:63–71

    Article  PubMed  CAS  Google Scholar 

  • Taylor FB, Russo J (2000) Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol 10:311–320

    PubMed  CAS  Google Scholar 

  • Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003) Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl) 165:260–269

    CAS  Google Scholar 

  • Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ (2004) Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 55:1031–1040

    Article  PubMed  CAS  Google Scholar 

  • Van Vliet SA, Jongsma MJ, Vanwersch RA, Philippens IH (2005) Human threat test: a method to test anxiety related behavior in a marmoset monkey. In: Proceedings of Measuring Behavior 2005. L. P. Noldus et al. (eds) Wageningen: Noldus Information Technology: 472–473

  • Ward CP, Harsh JR, York KM, Stewart KL, McCoy JG (2004) Modafinil facilitates performance on a delayed nonmatching to position swim task in rats. Pharmacol Biochem Behav 78:735–741

    Article  PubMed  CAS  Google Scholar 

  • Webster L, Andrews M, Stoddard G (2003) Modafinil treatment of opioid-induced sedation. Pain Med 4:135–140

    Article  PubMed  Google Scholar 

  • Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21:1787–1794

    PubMed  CAS  Google Scholar 

  • Woerner MG, Alvir JM, Saltz BL, Lieberman JA, Kane JM (1998) Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry 155:1521–1528

    PubMed  CAS  Google Scholar 

  • Wolthuis OL, Groen B, Philippens IH (1994) A simple automated test to measure exploratory and motor activity of marmosets. Pharmacol Biochem Behav 47:879–881

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Diagnosis and Therapy, TNO Defence, Security and Safety, Lange Kleiweg 137, 2288 GJ, Rijswijk, The Netherlands

    Sanneke A. M. van Vliet, Marjan J. Jongsma, Raymond A. P. Vanwersch & Ingrid H. C. H. M. Philippens

  2. Department of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands

    Sanneke A. M. van Vliet, Berend Olivier & Ingrid H. C. H. M. Philippens

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  1. Sanneke A. M. van Vliet
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  2. Marjan J. Jongsma
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  5. Ingrid H. C. H. M. Philippens
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Correspondence to Sanneke A. M. van Vliet.

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van Vliet, S.A.M., Jongsma, M.J., Vanwersch, R.A.P. et al. Behavioral effects of modafinil in marmoset monkeys. Psychopharmacology 185, 433–440 (2006). https://doi.org/10.1007/s00213-006-0340-4

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  • DOI: https://doi.org/10.1007/s00213-006-0340-4

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