title: S 18986 reverses spatial working memory impairments in aged mice: comparison with memantine.
abstract: BACKGROUND
  Normal or pathological ageing is characterized by working-memory dysfunction paired with a marked reduction in several neurotransmitters activity. The development of therapeutic strategy centered on the glutamatergic system known to bear a critical role in cognitive functions, is therefore of major importance in the treatment of mild forms of AD or age-related memory dysfunctions.
  
  
  OBJECTIVE
  In Experiment 1, we investigated the effects of ageing on spatial working memory measured by sequential alternation (SA). Thus, the decay of alternation rates over a series of trials separated by varying intertrial temporal intervals (ITI, from 5 sec to 180 sec) was studied in mice of different age groups. In Experiment 2, we investigated the memory-enhancing potential of S 18986--a modulator of AMPA receptors--on age-related SA impairments, in comparison with memantine--an antagonist of NMDA receptors--.
  
  
  RESULTS
  In Experiment 1, aged mice responded at chance with shorter ITI's and exhibited greater levels of interference in the SA task as compared to young adult mice. In Experiment 2, (1) S 18986 at 0.03 and 0.1 mg/kg reversed the memory deficit in aged mice but did not modify performance in young adult mice; (2) memantine at 10 mg/kg also increased SA rates in aged mice but did not improve performance in young adult mice.
  
  
  CONCLUSIONS
  The SA task is a useful tool to reveal age-induced time-dependent working memory impairments. As compared to memantine, S 18986--a compound targeting AMPA receptors--contributes a valuable therapy in the treatment of age-related cognitive dysfunctions or mild forms of AD.
authors.affiliation: Institut de Neurosciences Intégratives et Cognitives d'Aquitaine, Universités de Bordeaux, IMR CNRS 5287, Avenue des Facultés, 33405, Talence, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vandesquille
authors.forename: Ali
authors.initials: A
authors.lastname: Krazem
authors.forename: Caroline
authors.initials: C
authors.lastname: Louis
authors.forename: Pierre
authors.initials: P
authors.lastname: Lestage
authors.forename: Daniel
authors.initials: D
authors.lastname: Béracochéa
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000523:psychology; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001581:Benzothiadiazines / Q000008:administration & dosage / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D008569:Memory Disorders / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C414205:S18986-1; D008559:Memantine