%0 Journal Article
%T Chronotolerance study of the antiepileptic drug valproic acid in mice
%A Wafa Ben-Cherif
%A Ichrak Dridi
%A Karim Aouam
%A Mossadok Ben-Attia
%A Alain Reinberg
%A Naceur A Boughattas
%J Journal of Circadian Rhythms
%D 2012
%I BioMed Central
%R 10.1186/1740-3391-10-3
%X The influence of dosing-time on tolerance to VPA was investigated in 120 male Swiss mice synchronized under a light-dark cycle (12:12). The mean VPA lethal dose was first determined to be 850£¿¡À£¿0.2£¿mg/kg, i.p.. Such a dose was administered by i.p. route to a total of 90 mice divided in six circadian stages [1, 5, 9, 13, 17 and 21 Hours After Light Onset (HALO)] (15 mice/circadian time); 30 mice were used as control (5 mice / circadian time).The surviving treated mice exhibited a significant circadian variation in rectal temperature and body weight loss (p£¿<£¿0.001). The least rectal temperature change and body weight loss occurred when VPA was injected at 9 HALO. Drug dosing at 9 HALO resulted in -9£¿% weight loss whereas drug dosing at 17 HALO was -15£¿% (£¿£¿=£¿20.3 HALO£¿¡À£¿1.1£¿h, p£¿¡Ü£¿0.0001). Lethal toxicity also varied according to circadian dosing-time (¦Ö2£¿=£¿42.1, p£¿<£¿0.0001). The highest (60£¿%) and the lowest (6.67£¿%) survival rates were observed at 9 HALO and 17 HALO respectively. Cosinor analyses validated a significant circadian rhythm in survival duration with an acrophase at 8.4 HALO£¿¡À£¿0.75£¿h (p£¿<£¿0.001).With regards to these data the optimal tolerance to VPA occurred when the drug was administered in the second half of the light-rest span of mice which is physiologically analogous to the second half of the night for human patients.
%K Valproic acid
%K Chronotolerance
%K Circadian rhythm
%K Mice
%U http://www.jcircadianrhythms.com/content/10/1/3/abstract