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Prolonged intracerebroventricular infusion of neurosteroids affects cognitive performances in the mouse.
- Source :
-
Brain research [Brain Res] 2000 Mar 10; Vol. 858 (2), pp. 371-9. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- 5-alpha-Dihydroprogesterone
Animals
Behavior, Animal drug effects
Infusion Pumps, Implantable
Injections, Intraventricular
Male
Maze Learning drug effects
Memory drug effects
Mice
Pregnanediones metabolism
Prosencephalon drug effects
Prosencephalon metabolism
Space Perception drug effects
Cognition drug effects
Neuroprotective Agents pharmacology
Pregnanolone pharmacology
Pregnenolone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 858
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 10708689
- Full Text :
- https://doi.org/10.1016/s0006-8993(00)01953-3