Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors

Taku Nagai, Rina Murai, Kanae Matsui, Hiroyuki Kamei, Yukihiro Noda, Hiroshi Furukawa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Rationale: Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated. Objectives: In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly. Materials and methods: Mice were repeatedly administered PCP at a dose of 10mg/kg for 14days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0mg/kg) and haloperidol (0.3 and 1.0mg/kg) on cognitive impairment in mice treated with PCP repeatedly. Results: Single (1.0mg/kg) and repeated (0.03 and 0.1mg/kg, for 7days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT 1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole. Conclusions: These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.

Original languageEnglish
Pages (from-to)315-328
Number of pages14
JournalPsychopharmacology
Volume202
Issue number1-3
DOIs
Publication statusPublished - 01-01-2009
Externally publishedYes

Fingerprint

Phencyclidine
Receptor, Serotonin, 5-HT1A
Dopamine
Haloperidol
Schizophrenia
Raclopride
Dopamine D1 Receptors
Dopamine Antagonists
Recognition (Psychology)
Aripiprazole
Memory Disorders
Therapeutic Uses
Interpersonal Relations
Cognition
Antipsychotic Agents
Serotonin
Animal Models

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nagai, Taku ; Murai, Rina ; Matsui, Kanae ; Kamei, Hiroyuki ; Noda, Yukihiro ; Furukawa, Hiroshi ; Nabeshima, Toshitaka. / Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. In: Psychopharmacology. 2009 ; Vol. 202, No. 1-3. pp. 315-328.
@article{2f67d126fdf349b5a08f414b4e6c1837,
title = "Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors",
abstract = "Rationale: Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated. Objectives: In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly. Materials and methods: Mice were repeatedly administered PCP at a dose of 10mg/kg for 14days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0mg/kg) and haloperidol (0.3 and 1.0mg/kg) on cognitive impairment in mice treated with PCP repeatedly. Results: Single (1.0mg/kg) and repeated (0.03 and 0.1mg/kg, for 7days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT 1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole. Conclusions: These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.",
author = "Taku Nagai and Rina Murai and Kanae Matsui and Hiroyuki Kamei and Yukihiro Noda and Hiroshi Furukawa and Toshitaka Nabeshima",
year = "2009",
month = "1",
day = "1",
doi = "10.1007/s00213-008-1240-6",
language = "English",
volume = "202",
pages = "315--328",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "1-3",

}

Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. / Nagai, Taku; Murai, Rina; Matsui, Kanae; Kamei, Hiroyuki; Noda, Yukihiro; Furukawa, Hiroshi; Nabeshima, Toshitaka.

In: Psychopharmacology, Vol. 202, No. 1-3, 01.01.2009, p. 315-328.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors

AU - Nagai, Taku

AU - Murai, Rina

AU - Matsui, Kanae

AU - Kamei, Hiroyuki

AU - Noda, Yukihiro

AU - Furukawa, Hiroshi

AU - Nabeshima, Toshitaka

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Rationale: Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated. Objectives: In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly. Materials and methods: Mice were repeatedly administered PCP at a dose of 10mg/kg for 14days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0mg/kg) and haloperidol (0.3 and 1.0mg/kg) on cognitive impairment in mice treated with PCP repeatedly. Results: Single (1.0mg/kg) and repeated (0.03 and 0.1mg/kg, for 7days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT 1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole. Conclusions: These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.

AB - Rationale: Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated. Objectives: In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly. Materials and methods: Mice were repeatedly administered PCP at a dose of 10mg/kg for 14days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0mg/kg) and haloperidol (0.3 and 1.0mg/kg) on cognitive impairment in mice treated with PCP repeatedly. Results: Single (1.0mg/kg) and repeated (0.03 and 0.1mg/kg, for 7days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT 1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole. Conclusions: These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.

UR - http://www.scopus.com/inward/record.url?scp=59449096993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59449096993&partnerID=8YFLogxK

U2 - 10.1007/s00213-008-1240-6

DO - 10.1007/s00213-008-1240-6

M3 - Article

VL - 202

SP - 315

EP - 328

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 1-3

ER -