title: Effect of combined treatment with mirtazapine and risperidone on the MK-801-induced changes in the object recognition test in mice.
abstract: BACKGROUND
  Several clinical reports have suggested that the mirtazapine-induced augmentation of risperidone activity may effectively improve treatment of the negative and certain cognitive symptoms of schizophrenia.
  
  
  METHODS
  The aim of the present study was to evaluate the effect of mirtazapine and risperidone, given separately or jointly, on the impact of MK-801(an NMDA receptor antagonist), given prior to the first introductory session, on the object recognition memory in mice. To this end, we used the object recognition test in which animals were tested for the ability to discriminate between an old, familiar and a novel object. Mirtazapine (2.5 or 5 mg/kg) and risperidone (0.01 mg/kg) were given 30 min before MK-801, and MK-801 (0.1 or 0.2 mg/kg) was administered 30 min before the first introductory session. Memory retention was evaluated 1.5 h after the introductory session.
  
  
  RESULTS
  The obtained results showed that MK-801 (0.2 mg/kg) decreased memory retention when given before the introductory session. Co-treatment with risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) abolished the effect of MK-801, whereas those drugs given separately did not change the action of MK-801.
  
  
  CONCLUSIONS
  The obtained results suggest that mirtazapine may enhance the antipsychotic-like effect of risperidone in the animal test modeling some cognitive symptoms of schizophrenia. Further studies are necessary to elucidate its mechanism of action.
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.pl.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Rogóż
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D000078785:Mirtazapine; D009043:Motor Activity / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008803:Mianserin; D016291:Dizocilpine Maleate; D000078785:Mirtazapine; D018967:Risperidone