Pharmacology

Neuropharmacology

  • Professor: Mitsuhiro Yoshioka
  • Assistant Professor: Takayuki Yoshida
  • Assistant Professor: Yu Ohmura
  • Phone: +81-11-706-5059
  • FAX: +81-11-706-7872
  • E-mail: farmacol
The objectives of our department are to clarify the molecular basis of the neural circuits and the emotional behaviors regulated by the biogenic amines (especially, serotonin: 5-HT), focusing on the emotional function such as joy, anger, anxiety, fear and impulsivity using the electrophysiological, immunohistochemical, neurochemical and behavioral-pharmacological techniques. In addition, we investigate the pathogenesis of psychiatric disorders and evaluate the agents for psychiatric disorders using the animal models. We hope that these studies might provide the elucidation of the novel pharmacological mechanism and the development of therapeutic drugs for the psychiatric disorders by widely analyzing from a molecule to a behavior.

Research

1. Studies on functional roles in the serotonergic system

Serotonergic system plays important roles for the regulation of the emotional, cognitive and behavioral control processes in the central nervous system and for the pathogenesis related to emotional dysfunctions such as anxiety disorder, depression and schizophrenia. Based on these backgrounds, we investigate the functional role of the serotoninergic system in the pathogenesis of psychiatric disorders and the novel mechanism of the anxiolytics, antidepressants, antipsychotics and serotonin-related therapeutic drugs.

2. Development of animal models and novel therapeutic drugs for psychiatric disorders.

1) Early postnatal stress and emotional behaviors
Early negative life experience such as chronic neglect and maltreatment can lead to depression, anxiety disorders in human. Recent studies have focused on the serotonergic mechanism underlying regulation of emotional stress during the developmental period. We examined that traumatic events during early postnatal period would affect the serotonergic development, thereby the expression of emotional behaviors in the adult rats, focusing on the response to physiological stress.
2) Adolescent SHRSP/Ezo, an animal model for attention-deficit/hyperactivity disorder (ADHD)
ADHD is an early-onset neuropsychiatric disorder in children, symptomatically characterized by inattention and/or hyperactivity/impulsivity. We have proposed male adolescent stroke-prone spontaneously hypertensive rats (SHRSP/Ezo) as an appropriate animal model of ADHD. We investigate the pathogenesis of ADHD symptoms and explore the development of novel therapeutic drugs for ADHD using adolescent SHRSP/Ezo.

Education

[1] Pharmacology
[2] Intergrated pharmacology
[3] Pharmacology laboratory course

International Activities

Academic contribution

  • Yoshioka M: Councilor of The Serotonin Club, an international association for serotonin research.

Recent Invited Talks in International Conferences

  • Yoshioka M (2008) Stress and the serotonergic transmission in the cortico-limbic system, XXVI Collegium Internationale Neuro-Psychopharmacologicum Congress, Munich.
  • Yoshioka M (2008) Early postnatal stress disturbs normal development of the serotonergic neurons in the raphe nuclei, Collegium Internationale Neuro-Psychopharmacologicum Pacific-Asia Regional Meeting 2008, Kuala Lumpur.
  • Yoshioka M (2007) Early Postnatal Stress Produces a Lifelong Susceptibility to Emotional Events, The 33rd Congress on Science and Technology of Thailand, Bangkok.
  • Yoshioka M (2007) Early Postnatal Stress and the Serotonergic System, International Congress on 3rd Brain & Behaviour, Thessaloniki.
Fig1 Possible involvement of the serotonergic system of the synaptic transmission in the cortico-limbic system.
Fig2 Early postnatal stress and an age-related functional development of the rat.
Fig3 Behavioral and physiological validations of adolescent stroke-prone spontaneously hypertensive rats, SHRSP/Ezo, as an animal model of attention-deficit/hyperactivity disorder (ADHD).
Fig4 Lab members at Prof. Yoshioka's birthday in 2008.

Selected Publications

1. Hirata R, Matsumoto M, Judo C, Yamaguchi T, Izumi T, Yoshioka M, Togashi H: Possible relationship between the stress-induced synaptic response and metaplaticity in the hippocampal CA1 field of freely moving rats. Synapse, in press
2. Ohmura Y, Yamaguchi T, Izumi T, Matsumoto M, Yoshioka M (2008) Corticotropin releasing factor in the median raphe nucleus is involved in the retrieval of fear memory in rats. Eur J Pharmacol, 584(2-3):357-360
3. Konno K, Matsumoto M, Togashi H, Yamaguchi T, Izumi T, Watanabe M, Iwanaga T, Yoshioka M (2007) Early postnatal stress affects the serotonergic function in the median raphe nuclei of adult rats. Brain Res, 1172:60-66.
4. Matsumoto M, Higuchi K, Togashi H, Koseki H, Yamaguchi T, Kanno M, Yoshioka M (2005) Early postnatal stress alters the 5-HTergic modulation to emotional stress at postadolescent periods of rats. Hippocampus, 15(6):775-781.
5. Matsumoto M, Tachibana K, Togashi H, Tahara K, Kojima T, Yamaguchi T, Yoshioka M (2005) Chronic treatment with milnacipran reverses the impairment of synaptic plasticity induced by conditioned fear stress. Psychopharmacology (Berl), 179(3):606-612.
6. Jesmin S, Togashi H, Sakuma I, Mowa CN, Ueno K, Yamaguchi T, Yoshioka M, Kitabatake A (2004) Gonadal hormones and frontocortical expression of vascular endothelial growth factor in male stroke-prone, spontaneously hypertensive rats, a model for attention-deficit/hyperactivity disorder. Endocrinology, 145(9):4330-4343.
7. Ueno K, Togashi H, Matsumoto M, Ohashi S, Saito H, Yoshioka M (2002) α4β2 nicotinic acetylcholine receptor activation ameliorates impairment of spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder. J Pharmacol Exp Ther, 302(1):95-100.