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Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats.
Behav Brain Res. 2008 Jan 25; 186(2):197-207.BB

Abstract

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.

Authors+Show Affiliations

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.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17881065

Citation

Enomoto, Takeshi, et al. "Lurasidone Reverses MK-801-induced Impairment of Learning and Memory in the Morris Water Maze and Radial-arm Maze Tests in Rats." Behavioural Brain Research, vol. 186, no. 2, 2008, pp. 197-207.
Enomoto T, Ishibashi T, Tokuda K, et al. Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res. 2008;186(2):197-207.
Enomoto, T., Ishibashi, T., Tokuda, K., Ishiyama, T., Toma, S., & Ito, A. (2008). Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behavioural Brain Research, 186(2), 197-207.
Enomoto T, et al. Lurasidone Reverses MK-801-induced Impairment of Learning and Memory in the Morris Water Maze and Radial-arm Maze Tests in Rats. Behav Brain Res. 2008 Jan 25;186(2):197-207. PubMed PMID: 17881065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. AU - Enomoto,Takeshi, AU - Ishibashi,Tadashi, AU - Tokuda,Kumiko, AU - Ishiyama,Takeo, AU - Toma,Satoko, AU - Ito,Akira, Y1 - 2007/08/19/ PY - 2007/05/11/received PY - 2007/08/08/revised PY - 2007/08/10/accepted PY - 2007/9/21/pubmed PY - 2008/3/15/medline PY - 2007/9/21/entrez SP - 197 EP - 207 JF - Behavioural brain research JO - Behav Brain Res VL - 186 IS - 2 N2 - 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. SN - 0166-4328 UR - https://www.unboundmedicine.com/medline/citation/17881065/Lurasidone_reverses_MK_801_induced_impairment_of_learning_and_memory_in_the_Morris_water_maze_and_radial_arm_maze_tests_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(07)00423-8 DB - PRIME DP - Unbound Medicine ER -