Department of Psychiatry & Behavioral Sciences

Addictive Substance Project
Project Leader

Kazutaka IKEDA

Kazutaka Ikeda, the head of Department of Psychiatry and Behavioral Sciences since 2015, hasbeen the leader of the Addictive Substance Project since 2005. He graduated Faculty ofEngineering, the University of Tokyo in 1989. After that, he studied under Dr. Kenji Sobue, Dr.
Masayoshi Mishina and Dr. Toshiro Kumanishi as a graduate student. He received Doctor ofMedical Science in 1995 from Graduate School of Medical Science, Niigata University. He startedto work at RIKEN as a researcher under the supervision of Dr. Masao Ito, Dr Ryoji Yano and Dr
Hiroaki Niki in 1995. He moved to Tokyo Metropolitan Institute of Psychiatry in 2000 and has
leaded a project team since 2002. His current interest is to improve treatment, prevention, andunderstanding of addiction, pain, and developmental disorders through revealing of mechanisms
underlying addictive substance effects.
Research Summary
Staff
Researchers
Shinya KASAI
Daisuke NISHIZAWA
Masayo FUJITA
Soichiro IDE
Seii OHKA
Hiroko KOTAJIMA
Yuki MORIYA

Research Assistants
Yoko HAGINO
Junko HASEGAWA
Etsuko KAMEGAYA
Yukiko MATSUSHIMAYuki SERITA
Yuko EBATA
Kyoko NAKAYAMA

Students
Yuiko IKEKUBO
Yukiko OCHIAI
Yoshihisa KATO
Aimi YAMAGISHI

Yoshihiko KOSAKIMoe SOEDA
Rie INOUE
Shoka MATSUYAMA

Selected Publications
Fujita M, et al. (2020) “Increase in excitability ofhippocampal neurons during novelty-induced
hyperlocomotion in dopamine-deficient mice.” Mol.
Brain. 13: 126.

Addiction to various substances (e.g., drugs, alcohol, and tobacco) and behaviors(e.g., internet and gambling) is a serious public health problem. The use of illegal
drugs has been increasing in Japan in recent years. Thus, preventing and solving
problems that are related to addiction are important.
Some addictive drugs are also widely used as analgesics and for the treatment ofdevelopmental disorders. Some molecules that are involved in the actions ofaddictive drugs may be shared between analgesia and developmental disorders.
The goals of our project are the following:(1) Developing novel treatments for addiction and prevention. We study action
mechanisms of opioids, dopamine, and hallucinogens such as phencyclidine toreveal the onset of addiction using several mouse models and behavioral
pharmacological study. In parallel with the basic research, we also develop andverify a scale to addiction severity.
(2) Improving personalized pain treatment. Sensitivity of opioid analgesics is
associated with polymorphisms of several genes. Based on the genome information,
we develop personalized pain treatment.
(3) Developing novel treatments for developmental disorders. We mainly focus on
autism and attention deficit hyperactivity disorder (ADHD). In our project, tuberous
sclerosis complex 1 and 2 hetero knockout mouse and dopamine transporter
knockout mouse are mainly used as models of autism and ADHD, respectively. We
are finding novel treatments for autism.
Attaining these goals will make significant contributions to society. We seek toaccomplish these goals by studying the actions of addictive drugs using molecularbiological, behavioral pharmacological, human genomic, and clinical approaches.

Kotajima-Murakami H, et al. (2018) “Effects of
rapamycin on social interaction deficits and gene
expression in mice exposed to valproic acid inutero.” Mol. Brain 12:3
Sugaya N, et al. (2018) “A randomized controlled
study of the effect of ifenprodil on alcohol use inpatients with alcohol dependence.”
Neuropsychopharmacology Rep. 38(1):9-17.
Ide S and Ikeda K. (2018) “Mechanisms of theantidepressant effects of ketamine enantiomers
and their metabolites. ” Biol. Psychiatry. 84:551552.
Nishizawa D, et al. (2014) “Genome-wide
association study identifies a potent locus
associated with human opioid sensitivity.” Mol.
Psychiatry. 19: 55-62.
Sato A, et al. (2012) “Rapamycin reverses
impaired social interaction in mouse models oftuberous sclerosis complex” Nat. Commun. 3:
1292.

Trial and Error
Analgesia
Adverseside effects

Addiction

PainPain
Adverseside effects
Personalized Pain Management
PainPaintreatment

Developmentaldisorders

Three main project targets.

Geneticdiagnosis
Reducing
Increasing

MDMACannabisHallucinogen

Various addictive drugs.

Analgesic

Pain
Pain
Pain
Pre-diagnosis Pain Management

Drugs foradverse sideeffects

Scheme of personalized pain treatment strategy.
Laboratory HP: http://www.igakuken.or.jp/abuse/