The AMPA modulator S 18986 improves declarative and working memory performances in aged mice.
The aim of this study was to further characterize the memory-enhancing profile of S 18986 a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. S 18986 was studied in two mouse models of age-related memory deficits, using radial maze paradigms involving long-term/declarative memory and short-term/working memory. Aged mice exhibited severe deficits when compared with their younger counterparts in the two behavioural tests. S 18986 at the dose of 0.1 mg/kg selectively improved aged mouse performance in the test of long-term/declarative memory flexibility and exerted a beneficial effect on short-term retention of successive arm-visits in the short-term/working memory test. This study confirms the memory-enhancing properties of S 18986 and, in line with emerging data on multiple AMPA modulators, highlights the relevance of targeting AMPA receptors in the development of new memory enhancers.
Marighetto
Aline
A
Bordeaux 1-University, CNRS UMR 5228, Center of Cognitive and Integrative Neurosciences, Avenue des facultés, Talence, France.
Valerio
Stephane
S
Jaffard
Robert
R
Mormede
Cecile
C
Muñoz
Carmen
C
Bernard
Katy
K
Morain
Philippe
P
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001581:Benzothiadiazines / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy*; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism
D001581:Benzothiadiazines; D018091:Receptors, AMPA; C414205:S18986-1