First evidence of a delay-dependent working memory-enhancing effect of modafinil in mice

This study investigated the effects of pretest injection of modafinil on delayed spontaneous alternation rates (SA) used to evaluate working memory in C57 Bl/6 mice. In a first experiment, systemic modafinil at 64 mg/kg, but not at 8 mg/kg or 32 mg/kg doses produced a significant increase of alternation scores (intertrial interval (ITI) 60 s) when compared with controls. In a second experiment, modafinil (64 mg/kg) en- hanced the alternation rates mainly at long (60 s and 180 s) but not at short (5 s) ITIs. Exploratory latencies and activity in a four hole-board apparatus were not modified by modafinil administration. These experiments are the first to demonstrate a delay-dependent working memory-enhancing effect of modafinil.

[1]  L. Garma,et al.  Modafinil in obstructive sleep apnea-hypopnea syndrome: a pilot study in 6 patients. , 1997, Respiration; international review of thoracic diseases.

[2]  K. Fuxe,et al.  Effects of the vigilance promoting drug modafinil on the synthesis of GABA and glutamate in slices of rat hypothalamus , 1999, Neuroscience Letters.

[3]  J. Bizot Effects of Various Drugs Including Organophosphorus Compounds (OPC) and Therapeutic Compounds Against OPC on DRL Responding , 1998, Pharmacology Biochemistry and Behavior.

[4]  K. Fuxe,et al.  The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus , 1997, Neuroreport.

[5]  S. Nicolaidis,et al.  Nonamphetamine awakening agent modafinil induces feeding changes in the rat , 1993, Brain Research Bulletin.

[6]  K. Montgomery A test of two explanations of spontaneous alternation. , 1952, Journal of comparative and physiological psychology.

[7]  D. Batejat,et al.  Disrupted Sleep-Wake Rhythm and Performance: Advantages of Modafinil , 1995 .

[8]  J. O’Keefe Hippocampal function: does the working memory hypothesis work? Should we retire the cognitive map theory? , 1979 .

[9]  D. Batéjat,et al.  Interest of modafinil, a new psychostimulant, during a sixty‐hour sleep deprivation experiment , 1995, Fundamental & clinical pharmacology.

[10]  M. Jouvet,et al.  ネコ脳のアンフェタミン,メチルフェニデート,モダフィニルの覚醒作用における標的ニューロンのc‐fos免疫組織化学による検索 , 1996 .

[11]  F. Rambert,et al.  Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals. , 1990, European journal of pharmacology.

[12]  C. Piérard,et al.  Effects of a vigilance-enhancing drug, modafinil, on rat brain metabolism: 2D COSY 1H-NMR study , 1995, Brain Research.

[13]  J. Baranski,et al.  Modafinil, d‐amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature , 1995, Journal of sleep research.

[14]  E. Bullmore,et al.  Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil , 1999, Journal of sleep research.

[15]  D. Béracochéa,et al.  Effects of Ibotenic Lesions of Mammillary Bodies on Spontaneous and Rewarded Spatial Alternation in Mice , 1990, Journal of Cognitive Neuroscience.

[16]  M. Jouvet,et al.  Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[17]  M. Spedding,et al.  Contrasting EEG profiles elicited by antipsychotic agents in the prefrontal cortex of the conscious rat: antagonism of the effects of clozapine by modafinil , 1999, British journal of pharmacology.

[18]  P. Contreras,et al.  Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine , 1998, Neuroscience.

[19]  M. Jouvet,et al.  Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. , 1996, Proceedings of the National Academy of Sciences of the United States of America.