Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats.
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 1mg/kg p.o.), clozapine (3 and 10 mg/kg p.o.), aripiprazole (0.3 and 1mg/kg p.o.), and haloperidol (0.3 and 1mg/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.
Enomoto
Takeshi
T
Discovery Pharmacology II, Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 3-1-98, Kasugade Naka, Konohana-ku, Osaka 554-0022, Japan. takeshi-enomoto@ds-pharma.co.jp
Ishibashi
Tadashi
T
Tokuda
Kumiko
K
Ishiyama
Takeo
T
Toma
Satoko
S
Ito
Akira
A
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D054833:Isoindoles / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000188:drug therapy*; D000069056:Lurasidone Hydrochloride; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming; D013844:Thiazoles / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D054833:Isoindoles; D013844:Thiazoles; D016291:Dizocilpine Maleate; D000069056:Lurasidone Hydrochloride