Stress modulation of the memory retrograde-enhancing effects of the awakening drug modafinil in mice.
OBJECTIVE
This study investigated the dose-effect relationship of modafinil administration on contextual memory processes, in parallel with the measurements of plasma corticosterone levels in acutely stressed mice.


METHODS
Memory was first evaluated in normal (nonstressed) mice either in contextual (CSD) or spatial (SSD) tasks. Thus, C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board. The discriminations occurred on either distinct (CSD) or identical (SSD) floors (internal contextual cues). All mice received a vehicle intraperitoneal injection before learning and were injected 24 h later (20 min before the test session) either with vehicle or modafinil.


RESULTS
Results showed that modafinil-treated mice behaved similarly as vehicles in the spatial SSD task, whereas in contrast, memory of the first-learned discrimination (D1) in the CSD task was enhanced by a 32- but not a 16-mg/kg modafinil dose. Hence, we studied the effect of a pretest acute stress (electric footshocks) specifically on D1 performance in modafinil-treated subjects. Immediately after behavioral testing, blood was sampled to measure plasma corticosterone levels.


CONCLUSIONS
Results showed that: (1) stress significantly improved performance in vehicles, (2) stress decreased the efficiency threshold of modafinil, as performance was enhanced at the low dose (16 mg/kg), whereas this enhancement was obtained for the high dose (32 mg/kg) under nonstress conditions, (3) the performance was impaired at the high (32 mg/kg) dose, and (4) modafinil significantly reduced the magnitude of the stress-induced corticosterone secretion, mainly at the dose of 32 mg/kg.
Béracochéa
Daniel
D
CNIC (Centre de Neurosciences Intégratives et Cognitives), UMR CNRS 5228, Universités de Bordeaux 1 et 2, avenue des Facultés, 33405 Talence Cedex, France. d.beracochea@lnc.u-bordeaux1.fr
Liscia
Pierrette
P
Tronche
Christophe
C
Chauveau
Frédéric
F
Jouanin
Jean-Claude
JC
Piérard
Christophe
C
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects*; D001143:Arousal / Q000187:drug effects; D001245:Association Learning / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D009949:Orientation / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects; D013315:Stress, Psychological / Q000097:blood / Q000150:complications*; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil; D003345:Corticosterone