Effects of ziprasidone, SCH23390 and SB277011 on spatial memory in the Morris water maze test in naive and MK-801 treated mice

Pharmacol Biochem Behav. 2015 Nov;138:142-7. doi: 10.1016/j.pbb.2015.09.014. Epub 2015 Sep 21.

Abstract

Introduction: Patients with schizophrenia have cognitive dysfunctions; positive psychotic symptoms are the primary purposes for schizophrenia treatment. Improvements in cognitive function should be a characteristic of all newly developed drugs for the treatment of schizophreniawith dementia. Thus,we investigated the effects of the second-generation antipsychotic ziprasidone, dopamine D1 antagonist SCH-23390 and dopamine D3 antagonist SB-277011 on spatial learning and memory. Materials and methods: Male inbred mice were used. The effects of ziprasidone, SCH-23390 and SB-277011 were investigated using the Morris water maze test. Results: Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on the time spent in the target quadrant in naive mice.MK-801 (0.1mg/kg) significantly decreased the time spent in the target quadrant. The time spent in the target quadrant was significantly prolonged by Ziprasidone (0.5 and 1 mg/kg) and SCH-23390 (0.1 mg/kg), but not with SB-277011 (20 mg/kg) in MK-801-treated mice. Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on themean distance to the platformin naivemice.MK-801 significantly increased themean distance to the platform. Ziprasidone (1 mg/kg) and SCH-23390 (0.1 mg/kg) significantly decreased the mean distance to the platform in MK-801-treated mice, but SB-277011 (20 mg/kg) didn't. MK-801 significantly increased the total distance moved. Ziprasidone (0.5 and 1 mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on the total distance moved in naive mice. Ziprasidone (1 mg/kg) and SCH-23390 (0.1 mg/kg) significantly decreased the total distance moved in MK-801-treated mice, but SB-277011 (20 mg/kg) didn't. Conclusions: The second-generation antipsychotic drug ziprasidone and D1 antagonist SCH23390, but not the D3 antagonist SB277011, might be clinically useful for the treatment of cognitive impairments in patients with schizophrenia.

Keywords: Cognition; MK-801; Mice; Morris water maze; SB277011; SCH23390; Ziprasidone.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Benzazepines / pharmacology*
  • Dizocilpine Maleate / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Maze Learning / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Nitriles / pharmacology*
  • Piperazines / pharmacology*
  • Psychomotor Performance / drug effects
  • Spatial Memory / drug effects*
  • Tetrahydroisoquinolines / pharmacology*
  • Thiazoles / pharmacology*

Substances

  • Antipsychotic Agents
  • Benzazepines
  • Excitatory Amino Acid Antagonists
  • Nitriles
  • Piperazines
  • SB 277011
  • SCH 23390
  • Tetrahydroisoquinolines
  • Thiazoles
  • Dizocilpine Maleate
  • ziprasidone