Prolonged intracerebroventricular infusion of neurosteroids affects cognitive performances in the mouse.
The effects of prolonged intracerebroventricular (i.c.v.) steroid infusions on memory performances (Y-maze arm discrimination test) and on neurosteroids brain levels were studied in young adult male mice. The Y-maze test consisted of two trials separated by a time interval. In the first trial, one arm of the maze (subsequently called novel arm) was closed, and mice were allowed to visit the two accessible arms. After a short 2-h intertrial interval (ITI), control mice explored preferentially the novel arm, whereas with a longer 6-h ITI, they did not remember the location of the novel arm and performed at random level (33% of time spent in each arm). Using a 2-h ITI, allopregnanolone (THPROG, 0.5 and 1 ng/h) decreased memory performances to random level after 3 and 6 days of infusion. Conversely, with a 6-h ITI, pregnenolone sulfate (PREG S, 10, 50, and 100 ng/h) significantly increased memory performances after 3 days, but only the smallest dose was still effective after 6 days. THPROG infusion (1 ng/h) increased the forebrain concentration of 5alpha-dihydroprogesterone (DHPROG) and tended to increase its own level. PREG S administration (10 ng/h) increased its own concentration and tended to increase those of pregnenolone (PREG) and of further metabolites. In conclusion, the memory-enhancing effects of PREG S and the inhibitory ones of THPROG have been confirmed. A persistent, however moderate, increase of PREG S brain concentration might be of interest for the treatment of amnesic deficits.
Ladurelle
N
N
Laboratoire "Stéroïdes et Système Nerveux: Physiopathologie Moléculaire et Clinique", U488 INSERM, 80 rue du Général Leclerc, 94276, Le Kremlin-Bicêtre, France.
Eychenne
B
B
Denton
D
D
Blair-West
J
J
Schumacher
M
M
Robel
P
P
Baulieu
E
E
D043582:5-alpha-Dihydroprogesterone; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011277:Pregnanediones / Q000378:metabolism; D011280:Pregnanolone / Q000494:pharmacology*; D011284:Pregnenolone / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects
D018696:Neuroprotective Agents; D011277:Pregnanediones; C018370:pregnenolone sulfate; D011284:Pregnenolone; D043582:5-alpha-Dihydroprogesterone; D011280:Pregnanolone