title: Effects of low-dose D-serine on recognition and working memory in mice.
abstract: BACKGROUND
  D -Serine is an endogenous co-agonist of the N-methyl-D: -aspartate (NMDA) receptor and has been suggested to improve cognitive deficits in schizophrenia.
  
  
  OBJECTIVE
  The present study investigates the effects of treatment with D -serine in mice on tasks that require recognition learning and working memory, two cognitive domains that are impaired in schizophrenia.
  
  
  METHODS
  We studied the effects of various regimens of systemic administration of D -serine (50 mg/kg/day) on BALB/c mice performing object recognition, T-maze alternation, and open-field exploration tasks. For the object recognition task, we also contrasted the effects of D -serine and D -cycloserine and investigated whether D -serine could reverse alterations induced by subchronic injections of the NMDA antagonist MK-801. D -Serine levels after injections were measured by high-performance liquid chromatography.
  
  
  RESULTS
  In the object recognition task, pre-training treatment with D -serine or D -cycloserine significantly enhanced recognition memory 24 h after training. A single administration of D -serine 30 min (but not 6 h) after training produced similar enhancement, suggesting an effect on memory consolidation. Daily treatment with D: -serine enhanced both object recognition and T-maze performance over multiple days and improved short-term memory in MK-801-treated mice. D -Serine treatment did not alter open-field exploration. Behavioral effects were accompanied by increased levels of D -serine in the hippocampus of treated animals.
  
  
  CONCLUSIONS
  Our results show that treatment with D -serine can improve performance in tasks related to recognition learning and working memory, suggesting that this agent can be useful for the treatment of disorders involving declines in these cognitive domains.
authors.affiliation: Instituto de Ciências Biomédicas, CCS, sala F1-03, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bado
authors.forename: Caroline
authors.initials: C
authors.lastname: Madeira
authors.forename: Charles
authors.initials: C
authors.lastname: Vargas-Lopes
authors.forename: Thiago C
authors.initials: TC
authors.lastname: Moulin
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Wasilewska-Sampaio
authors.forename: Luise
authors.initials: L
authors.lastname: Maretti
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: de Oliveira
authors.forename: Olavo B
authors.initials: OB
authors.lastname: Amaral
authors.forename: Rogério
authors.initials: R
authors.lastname: Panizzutti
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003523:Cycloserine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D012694:Serine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D016291:Dizocilpine Maleate; D003523:Cycloserine