Strategy to develop a new drug for treatment-resistant depression - Role of electroconvulsive stimuli and BDNF

Bingjin Li, Katsuya Suemaru, Yoshihisa Kitamura, Ranji Cui, Yutaka Gomita, Hiroaki Araki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In recent years, depression studies have focused on morphological changes associated with depression. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that plays an important role in the morphological changes associated with depression and the mechanisms of antidepressants. On the other hand, hyperfunction of the hypothalamic-pituitary-adrenal axis has been link to pathophysiology of depression. In our previous studies, ACTH-treated rats served as a valuable animal model of tricyclic antidepressant-resistant depressive conditions. However, few neuroanatomic studies have been done. In the present study, we investigated mechanisms underling ACTH-treated rat serving an imipramine treatment-resistant depression model using c-Fos as a marker. The c-Fos immunohistochemical study indicated that the medial prefrontal cortex is an action site of imipramine in ACTH-treated rats. Electroconvulsive therapy is considered an effective treatment for treatment-resistant depression. However, the mechanisms causing treatment-resistant depressive conditions are unknown. We investigated the effect of repeated electrical convulsive shock (ECS)-treatment using the forced swim test, a screening method for antidepressant-like activity, and hippocampal BDNF protein levels in ACTH-treated rats. Findings showed that repeated ECS treatment decreased the immobility time during forced swim test. Furthermore, the ECS treatment also markedly increased the hippocampal BDNF levels in the rat tricyclic antidepressant-resistant depression model. In addition, the repeated ECS treatment showed long-lasting effects on forced swim test and increased of hippocampal BDNF levels in normal rats. These findings suggest that BDNF plays a key role in the antidepressant-like effect of ECS and that increased BDNF may be involved in promoting the longlasting effect.

Original languageEnglish
Pages (from-to)735-742
Number of pages8
JournalYakugaku Zasshi
Volume127
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Treatment-Resistant Depressive Disorder
Brain-Derived Neurotrophic Factor
Shock
Adrenocorticotropic Hormone
Depression
Pharmaceutical Preparations
Antidepressive Agents
Imipramine
Tricyclic Antidepressive Agents
Nerve Growth Factors
Electroconvulsive Therapy
Prefrontal Cortex
Animal Models

Keywords

  • Antidepressant
  • Brain-derived neurotrophic factor (BDNF)
  • Electrical convulsive shock
  • Hypothalamic-pituitary-adrenal (HPA) axis
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Strategy to develop a new drug for treatment-resistant depression - Role of electroconvulsive stimuli and BDNF. / Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Cui, Ranji; Gomita, Yutaka; Araki, Hiroaki.

In: Yakugaku Zasshi, Vol. 127, No. 4, 04.2007, p. 735-742.

Research output: Contribution to journalArticle

Li, Bingjin ; Suemaru, Katsuya ; Kitamura, Yoshihisa ; Cui, Ranji ; Gomita, Yutaka ; Araki, Hiroaki. / Strategy to develop a new drug for treatment-resistant depression - Role of electroconvulsive stimuli and BDNF. In: Yakugaku Zasshi. 2007 ; Vol. 127, No. 4. pp. 735-742.
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