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

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.

• Authors: Pelin Tanyeri, Mehmet Emin Buyukokuroglu, Oguz Mutlu, Güner Ulak, Füruzan Yildiz Akar, Ipek Komsuoglu Celikyurt, Bekir Faruk Erden
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 138 Pg. 142-7 (Nov 2015) ISSN: 1873-5177 [Electronic] United States
• PMID: 26394282 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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)