Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects

Yu Ohmura, Iku Tsutsui-Kimura, Hitomi Sasamori, Mao Nebuka, N. Nishitani, Kenji Tanaka, Akihiro Yamanaka, Mitsuhiro Yoshioka

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Serotonergic agents have been widely used for treatment of psychiatric disorders, but the therapeutic effects are insufficient and these drugs often induce severe side effects. We need to specify the distinct serotonergic pathways underlying each mental function to overcome these problems. Preclinical studies have demonstrated that the central serotonergic system is involved in several emotional/cognitive functions including anxiety, depression, and impulse control, but it remains unclear whether each function is regulated by a different serotonergic system. We used optogenetic strategy to increase central serotonergic activity in mice and evaluated the behavioral consequences. Pharmacological and genetic tools were used to determine the subtype of 5-HT receptors responsible for the observed effects. We demonstrated that the serotonergic activation in the median raphe nucleus enhanced anxiety-like behavior, the serotonergic activation in the dorsal raphe nucleus exerted antidepressant-like effects, and the serotonergic activation in the median or dorsal raphe nucleus suppressed impulsive action. We also found that different serotonergic terminals, ventral hippocampus, ventral tegmental area/substantia nigra, and subthalamic/parasubthalamic nucleus, are involved in regulating anxiety-like behavior, antidepressant-like, and anti-impulsive effects, respectively. Furthermore, we found, using triple-transgenic mice, that the stimulation of the 5-HT2C receptor is required to evoke anxiety-like behavior, but not to exert anti-impulsive effects. These results suggest the need for pathway-specific treatments and provide important insights that will help the development of more effective and safer therapeutics.

Original languageEnglish
Article number107703
JournalNeuropharmacology
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Antidepressive Agents
Anxiety
Optogenetics
Serotonin Agents
Subthalamic Nucleus
Ventral Tegmental Area
Raphe Nuclei
Serotonin Receptors
Therapeutic Uses
Substantia Nigra
Cognition
Transgenic Mice
Psychiatry
Hippocampus
Pharmacology
Depression
Pharmaceutical Preparations
Dorsal Raphe Nucleus
Therapeutics

Keywords

  • Emotion
  • Impulsive action
  • Optogenetics
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects. / Ohmura, Yu; Tsutsui-Kimura, Iku; Sasamori, Hitomi; Nebuka, Mao; Nishitani, N.; Tanaka, Kenji; Yamanaka, Akihiro; Yoshioka, Mitsuhiro.

In: Neuropharmacology, 01.01.2019.

Research output: Contribution to journalArticle

Ohmura, Yu ; Tsutsui-Kimura, Iku ; Sasamori, Hitomi ; Nebuka, Mao ; Nishitani, N. ; Tanaka, Kenji ; Yamanaka, Akihiro ; Yoshioka, Mitsuhiro. / Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects. In: Neuropharmacology. 2019.
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