Improvement of episodic contextual memory by S 18986 in middle-aged mice: comparison with donepezil.
BACKGROUND
This study compared the effects of S 18986, a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, to those of donepezil a cholinesterase inhibitor on memory impairments induced by ageing in a contextual serial discrimination (CSD) task in middle-aged mice.


METHODS
The CSD task involved the learning of two consecutive discriminations in a four-hole board, each performed on two different floors. This model has been developed to study simultaneously different forms of memory in mice (i.e., episodic-like vs semantic-like forms of memory). We showed that placebo-middle-aged mice (14-15 months old) and placebo-aged subjects (19-20 months old) exhibited a severe memory deficit for the first but not the second discrimination, which was due to an increase in interference, as compared with placebo-treated young mice (5 months old). Middle-aged mice were given (9 days) per os administration of either donepezil, S 18986, or placebo.


CONCLUSIONS
Both 0.3 mg/kg donepezil and 0.1 mg/kg S 18986 reversed the deficit of middle-aged mice through a significant increase in contextually correct responses and in parallel a tendency to reduce interfering responses.


CONCLUSIONS
Overall, S 18986 emerges as having a beneficial impact on contextual memory processes in middle-aged mice.
Béracochéa
D
D
Centre de Neurosciences Intégratives et Cognitives(CNIC), UMR CNRS 5228, Bat Biologie Animale, Univ. Bordeaux 1 et 2, 33405, Talence-cedex, France. d.beracochea@lnc.u-bordeaux1.fr
Philippin
J N
JN
Meunier
S
S
Morain
P
P
Bernard
K
K
D000375:Aging / Q000523:psychology*; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D010880:Piperidines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000378:metabolism*; D012153:Retention, Psychology / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects
D001581:Benzothiadiazines; D007189:Indans; D010880:Piperidines; D018091:Receptors, AMPA; C414205:S18986-1; D000077265:Donepezil