Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice.
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.
Piérard
Christophe
C
Institut de Médecine Aérospatiale du Service de Santé des Armées, France. cpierard@imassa.fr
Liscia
Pierrette
P
Philippin
Jean-Nicolas
JN
Mons
Nicole
N
Lafon
Thierry
T
Chauveau
Frédéric
F
Van Beers
Pascal
P
Drouet
Isabelle
I
Serra
André
A
Jouanin
Jean-Claude
JC
Béracochéa
Daniel
D
D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004569:Electroencephalography / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D000077408:Modafinil; D011597:Psychomotor Performance / Q000187:drug effects*; D012892:Sleep Deprivation / Q000188:drug therapy* / Q000523:psychology*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil