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The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone.
Behav Brain Res. 2011 Jun 20; 220(1):83-90.BB

Abstract

We have previously reported that lurasidone, a novel atypical antipsychotic with potent serotonin 5-HT(7) antagonist and 5-HT(1A) partial agonist activities, is superior to other antipsychotics in improving the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801-induced learning and memory impairment in the passive avoidance (PA) and Morris water maze (MWM) tests in rats. In this study, we investigated the effects of selective antagonists of 5-HT(7) and 5-HT(1A) receptors (SB-656104-A and WAY-100635, respectively) on MK-801-induced learning and memory impairment in the same tests. In the PA test, either pre-training (3 and 10mg/kg, p.o.) or post-training (0.3mg/kg, i.v.) administration of lurasidone significantly reversed the test response impaired by MK-801, consistent with our previous reports. Pre-training administration of either SB-656104-A (10 and 30 mg/kg, i.p.) or WAY-100635 (1mg/kg, s.c.) also significantly reversed MK-801-induced memory impairment. Furthermore, post-training administration of either SB-656104-A (0.3mg/kg, i.v.) or WAY-100635 (0.01 mg/kg, i.v.) counteracted the effect of MK-801, which suggested that both 5-HT receptor subtype-selective antagonists could restore the memory consolidation process. In the MWM test, SB-656104-A (3mg/kg, i.p.) reversed learning impairment induced by MK-801. On the other hand, WAY-100635 (0.3 and 1mg/kg, i.p.) did not have any effect on the MK-801-induced learning impairment. Taken together, our results showed that 5-HT(7) and 5-HT(1A) receptor antagonists mimic the effect of lurasidone in whole or in part, respectively, to reverse MK-801-induced learning and memory impairment, which warrants further investigation of the interaction of lurasidone with these serotonin receptors as a possible mechanism underlying its procognitive effects in these animal models.

Authors+Show Affiliations

Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21277905

Citation

Horisawa, Tomoko, et al. "The Effects of Selective Antagonists of Serotonin 5-HT7 and 5-HT1A Receptors On MK-801-induced Impairment of Learning and Memory in the Passive Avoidance and Morris Water Maze Tests in Rats: Mechanistic Implications for the Beneficial Effects of the Novel Atypical Antipsychotic Lurasidone." Behavioural Brain Research, vol. 220, no. 1, 2011, pp. 83-90.
Horisawa T, Ishibashi T, Nishikawa H, et al. The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone. Behav Brain Res. 2011;220(1):83-90.
Horisawa, T., Ishibashi, T., Nishikawa, H., Enomoto, T., Toma, S., Ishiyama, T., & Taiji, M. (2011). The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone. Behavioural Brain Research, 220(1), 83-90. https://doi.org/10.1016/j.bbr.2011.01.034
Horisawa T, et al. The Effects of Selective Antagonists of Serotonin 5-HT7 and 5-HT1A Receptors On MK-801-induced Impairment of Learning and Memory in the Passive Avoidance and Morris Water Maze Tests in Rats: Mechanistic Implications for the Beneficial Effects of the Novel Atypical Antipsychotic Lurasidone. Behav Brain Res. 2011 Jun 20;220(1):83-90. PubMed PMID: 21277905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone. AU - Horisawa,Tomoko, AU - Ishibashi,Tadashi, AU - Nishikawa,Hiroyuki, AU - Enomoto,Takeshi, AU - Toma,Satoko, AU - Ishiyama,Takeo, AU - Taiji,Mutsuo, Y1 - 2011/01/26/ PY - 2010/11/11/received PY - 2011/01/14/revised PY - 2011/01/19/accepted PY - 2011/2/1/entrez PY - 2011/2/1/pubmed PY - 2011/7/16/medline SP - 83 EP - 90 JF - Behavioural brain research JO - Behav Brain Res VL - 220 IS - 1 N2 - We have previously reported that lurasidone, a novel atypical antipsychotic with potent serotonin 5-HT(7) antagonist and 5-HT(1A) partial agonist activities, is superior to other antipsychotics in improving the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801-induced learning and memory impairment in the passive avoidance (PA) and Morris water maze (MWM) tests in rats. In this study, we investigated the effects of selective antagonists of 5-HT(7) and 5-HT(1A) receptors (SB-656104-A and WAY-100635, respectively) on MK-801-induced learning and memory impairment in the same tests. In the PA test, either pre-training (3 and 10mg/kg, p.o.) or post-training (0.3mg/kg, i.v.) administration of lurasidone significantly reversed the test response impaired by MK-801, consistent with our previous reports. Pre-training administration of either SB-656104-A (10 and 30 mg/kg, i.p.) or WAY-100635 (1mg/kg, s.c.) also significantly reversed MK-801-induced memory impairment. Furthermore, post-training administration of either SB-656104-A (0.3mg/kg, i.v.) or WAY-100635 (0.01 mg/kg, i.v.) counteracted the effect of MK-801, which suggested that both 5-HT receptor subtype-selective antagonists could restore the memory consolidation process. In the MWM test, SB-656104-A (3mg/kg, i.p.) reversed learning impairment induced by MK-801. On the other hand, WAY-100635 (0.3 and 1mg/kg, i.p.) did not have any effect on the MK-801-induced learning impairment. Taken together, our results showed that 5-HT(7) and 5-HT(1A) receptor antagonists mimic the effect of lurasidone in whole or in part, respectively, to reverse MK-801-induced learning and memory impairment, which warrants further investigation of the interaction of lurasidone with these serotonin receptors as a possible mechanism underlying its procognitive effects in these animal models. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21277905/The_effects_of_selective_antagonists_of_serotonin_5_HT7_and_5_HT1A_receptors_on_MK_801_induced_impairment_of_learning_and_memory_in_the_passive_avoidance_and_Morris_water_maze_tests_in_rats:_mechanistic_implications_for_the_beneficial_effects_of_the_novel_atypical_antipsychotic_lurasidone_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00074-X DB - PRIME DP - Unbound Medicine ER -