Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex

Nobuaki Egashira, Katsunori Iwasaki, Ayumi Ishibashi, Kazuhide Hayakawa, Ryoko Okuno, Moe Abe, Naoki Uchida, Kenichi Mishima, Kotaro Takasaki, Ryoji Nishimura, Ryozo Oishi, Michihiro Fujiwara

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

Original languageEnglish
Pages (from-to)1516-1520
Number of pages5
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume32
Issue number6
DOIs
Publication statusPublished - Aug 1 2008

Fingerprint

Serotonin Receptors
Behavioral Symptoms
Prefrontal Cortex
Dementia
Receptor, Serotonin, 5-HT2A
Head
Psychology
Serotonin
Alzheimer Disease
Traditional Medicine
Caregivers
Yi-Gan San
Therapeutics
Placebos
Quality of Life
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biological Psychiatry

Cite this

Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. / Egashira, Nobuaki; Iwasaki, Katsunori; Ishibashi, Ayumi; Hayakawa, Kazuhide; Okuno, Ryoko; Abe, Moe; Uchida, Naoki; Mishima, Kenichi; Takasaki, Kotaro; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 32, No. 6, 01.08.2008, p. 1516-1520.

Research output: Contribution to journalArticle

Egashira, Nobuaki ; Iwasaki, Katsunori ; Ishibashi, Ayumi ; Hayakawa, Kazuhide ; Okuno, Ryoko ; Abe, Moe ; Uchida, Naoki ; Mishima, Kenichi ; Takasaki, Kotaro ; Nishimura, Ryoji ; Oishi, Ryozo ; Fujiwara, Michihiro. / Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2008 ; Vol. 32, No. 6. pp. 1516-1520.
@article{d2e6d625d6114966bf26228a5f0b20db,
title = "Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex",
abstract = "Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.",
author = "Nobuaki Egashira and Katsunori Iwasaki and Ayumi Ishibashi and Kazuhide Hayakawa and Ryoko Okuno and Moe Abe and Naoki Uchida and Kenichi Mishima and Kotaro Takasaki and Ryoji Nishimura and Ryozo Oishi and Michihiro Fujiwara",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.pnpbp.2008.05.010",
language = "English",
volume = "32",
pages = "1516--1520",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex

AU - Egashira, Nobuaki

AU - Iwasaki, Katsunori

AU - Ishibashi, Ayumi

AU - Hayakawa, Kazuhide

AU - Okuno, Ryoko

AU - Abe, Moe

AU - Uchida, Naoki

AU - Mishima, Kenichi

AU - Takasaki, Kotaro

AU - Nishimura, Ryoji

AU - Oishi, Ryozo

AU - Fujiwara, Michihiro

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

AB - Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

UR - http://www.scopus.com/inward/record.url?scp=47749127667&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47749127667&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2008.05.010

DO - 10.1016/j.pnpbp.2008.05.010

M3 - Article

VL - 32

SP - 1516

EP - 1520

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

IS - 6

ER -