Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice

• Published in: Pharmacology, biochemistry and behavior Vol. 88; no. 1; pp. 55 - 63
• Main Authors: Piérard, Christophe, Liscia, Pierrette, Philippin, Jean-Nicolas, Mons, Nicole, Lafon, Thierry, Chauveau, Frédéric, Van Beers, Pascal, Drouet, Isabelle, Serra, André, Jouanin, Jean-Claude, Béracochéa, Daniel
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2007; Elsevier Science
• Subjects: Animals; Benzhydryl Compounds - therapeutic use; Biological and medical sciences; Central Nervous System Stimulants - therapeutic use; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Electroencephalography - drug effects; Genes, fos - genetics; Immunohistochemistry; Maze Learning - drug effects; Medical sciences; Memory; Memory - drug effects; Mice; Modafinil; Nervous system (semeiology, syndromes); Neural activity; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Sleep deprivation; Sleep Deprivation - drug therapy; Sleep Deprivation - psychology; Modafinil; Neural activity; Memory; Sleep deprivation; Nervous system diseases; CNS stimulant; Psychotropic; Rodentia; Sleep disorder; Vertebrata; Mammalia; Sleep; Mouse; Insomnia; Animal; Neurological disorder; Performance
• ISSN: 0091-3057
• DOI: 10.1016/j.pbb.2007.07.006

The original aims of our study have been to investigate in sleep-deprived mice, the effects of modafinil administration on spatial working memory, in parallel with the evaluation of neural activity level, as compared to non-sleep-deprived animals. For this purpose, an original sleep deprivation apparatus was developed and validated with continuous electroencephalography recording. Memory performance was evaluated using spontaneous alternation in a T-maze, whereas the neural activity level was estimated by the quantification of the c-Fos protein in various cerebral zones. This study allowed altogether: First, to evidence that a diurnal 10-h sleep deprivation period induced an impairment of spatial working memory. Second, to observe a decrease in c-Fos expression after sleep deprivation followed by a behavioural test, as compared to non-sleep-deprived mice. This impairment in neural activity was evidenced in areas involved in wake–sleep cycle regulation (anterior hypothalamus and supraoptic nucleus), but also in memory (frontal cortex and hippocampus) and emotions (amygdala). Finally, to demonstrate that modafinil 64 mg/kg is able to restore on the one hand memory performance after a 10-h sleep deprivation period, and on the other hand, the neural activity level in the very same brain areas where it was previously impaired by sleep deprivation and cognitive task.