Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test.
Lurasidone (SM-13496) is a novel atypical antipsychotic with high affinities to dopamine D2, serotonin 5-HT7, 5-HT2A, 5-HT1A receptors and alpha2C adrenoceptor. In this study, the effects of lurasidone on the rat passive-avoidance response and its impairment by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) were evaluated and compared with those of other antipsychotics. The passive-avoidance response was examined by measuring the step-through latency, 1 day after the animals received foot-shock training. When given before the training session, lurasidone did not affect the passive-avoidance response at any dose tested (1-30 mg/kg, p.o.). All the other atypical antipsychotics examined (i.e., risperidone, olanzapine, quetiapine, clozapine and aripiprazole), however, significantly reduced the step-through latency at relatively high doses. A pre-training administration of lurasidone significantly and dose-dependently reversed the MK-801-induced impairment of the passive-avoidance response. At doses lower than those that affected the passive-avoidance response, risperidone, quetiapine, and clozapine partially reduced the MK-801-induced impairment, whereas haloperidol, olanzapine, and aripiprazole were inactive. In addition, the post-training administration of lurasidone was as effective in countering the MK-801 effect as the pre-training administration, suggesting that lurasidone worked, at least in part, by restoring the memory consolidation process disrupted by MK-801. These results suggest that lurasidone is superior to other antipsychotics in improving the MK-801-induced memory impairment and may be clinically useful for treating cognitive impairments in schizophrenia.
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd, Osaka, Japan. takeo-ishiyama@ds-pharma.co.jp
Takeo
T
Ishiyama
Kumiko
K
Tokuda
Tadashi
T
Ishibashi
Akira
A
Ito
Satoko
S
Toma
Yukihiro
Y
Ohno
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000633:toxicity*; D065127:Dopamine D2 Receptor Antagonists; D054833:Isoindoles / Q000494:pharmacology*; D000069056:Lurasidone Hydrochloride; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D058830:Serotonin 5-HT2 Receptor Antagonists; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D054833:Isoindoles; D058830:Serotonin 5-HT2 Receptor Antagonists; D013844:Thiazoles; D016291:Dizocilpine Maleate; D000069056:Lurasidone Hydrochloride