Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats

• Published in: Behavioural brain research Vol. 186; no. 2; pp. 197 - 207
• Main Authors: Enomoto, Takeshi, Ishibashi, Tadashi, Tokuda, Kumiko, Ishiyama, Takeo, Toma, Satoko, Ito, Akira
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 25.01.2008; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Antipsychotic Agents - therapeutic use; Antipsychotics; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Isoindoles - therapeutic use; Learning and memory; Learning Disorders - chemically induced; Learning Disorders - drug therapy; Lurasidone Hydrochloride; Male; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Morris water maze; Neuropharmacology; NMDA receptor antagonist; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Radial-arm maze; Rats; Rats, Wistar; Reaction Time - drug effects; Schizophrenia; Swimming; Thiazoles - therapeutic use; Learning and memory; Schizophrenia; Antipsychotics; Morris water maze; NMDA receptor antagonist; Radial-arm maze; Rat; Neuroleptic; Psychotropic; Memory; Glutamate receptor; Space perception; Psychosis; Acquisition process; Antipsychotic; Antagonist; Dizocilpine; Rodentia; Neuroprotective agent; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Lurasidone; Perceptive learning; NMDA receptor; Arm
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2007.08.012

We have previously shown that lurasidone, a novel atypical antipsychotic, potently reverses learning impairment induced by the N-methyl- d-aspartate receptor antagonist MK-801 in the rat passive avoidance test. However, the effects of lurasidone in other learning and memory tasks remain to be investigated. We investigated the effects of lurasidone and other marketed antipsychotics (risperidone, clozapine, aripiprazole, and haloperidol) on MK-801-induced impairment of learning and memory in the Morris water maze (MWM) and radial-arm maze (RAM) tests in rats. Learning and memory impairment in the MWM test, as measured by escape latency, escape distance, and diving behavior, and in the RAM test, as measured by reference and working memory errors, was induced by MK-801 (i.p.) at doses of 0.15 and 0.2 mg/kg, respectively. In the MWM test, lurasidone (1 and 3 mg/kg p.o.) potently reversed MK-801-induced learning impairment. In the RAM test, lurasidone (1 and 3 mg/kg p.o.) potently reversed MK-801-induced reference memory impairment and moderately but not significantly attenuated MK-801-induced working memory impairment. Risperidone (0.3 and 1 mg/kg p.o.), clozapine (3 and 10 mg/kg p.o.), aripiprazole (0.3 and 1 mg/kg p.o.), and haloperidol (0.3 and 1 mg/kg p.o.) did not reverse MK-801-induced impairment of learning and memory in both tasks. Lurasidone, but not the other antipsychotics tested in this study, reverses MK-801-induced impairment of learning and memory in both the MWM test and the RAM test. These results suggest that lurasidone would be more effective in treating schizophrenics with cognitive dysfunction than current antipsychotics.