Related Experiment Video

Updated: May 24, 2026

Restraint to Induce Stress in Mice and Rats
03:48

Restraint to Induce Stress in Mice and Rats

Published on: December 6, 2024

Changes in the orexin system, hypothalamic-pituitary-adrenal axis and circadian rhythm in juvenile-stressed rats

Kazune Ozaki1, Shinya Nishiide2, Hiroki Shikanai3

  • 1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.

Journal of Pharmacological Sciences
|May 22, 2026
PubMed

Insights

Stress-induced depression in rats altered the orexin system, particularly in the hippocampus. Targeting orexin receptors in the hippocampus may offer new antidepressant strategies by modulating stress responses.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Endocrinology

Background:

  • The orexin system regulates feeding, sleep, and autonomic functions.
  • Orexin receptor antagonists are used as hypnotics and show promise for treating major depressive disorder.

Purpose of the Study:

  • To investigate the orexin system's role in a rat model of depression induced by juvenile stress (3-week foot shock).
  • To explore the hippocampus as a potential target for antidepressant effects of orexin receptor antagonists.

Main Methods:

  • Utilized a juvenile stress rat model (3-week foot shock).
  • Measured prepro-orexin mRNA, orexin A protein, orexin receptor type 1 mRNA, and protein levels in the hypothalamus and dorsal hippocampus.
  • Administered orexin receptor antagonists (SB334867 and TCS OX2 29) into the dorsal hippocampus of naïve rats.
  • Assessed depressive-like behaviors, hypothalamus-pituitary-adrenal axis activity, body temperature variations, and behavioral activity.

Main Results:

  • Juvenile-stressed rats showed reduced hypothalamic prepro-orexin mRNA but increased dorsal hippocampal orexin receptor type 1 mRNA and protein.
  • Hippocampal microinjection of orexin receptor antagonists reduced depressive-like behaviors in naïve rats.
  • Stressed rats exhibited HPA axis enhancement, reduced daily body temperature variation, and increased activity.

Conclusions:

  • Juvenile stress alters orexin system components, particularly increasing orexin receptor type 1 in the dorsal hippocampus.
  • The dorsal hippocampus is identified as a key brain region mediating the antidepressant effects of orexin receptor antagonists.
  • Targeting hippocampal orexin receptors may represent a novel therapeutic approach for depression.
Keywords:
Animal modelHippocampusMajor depressive disorder (MDD)OrexinOrexin receptor antagonist

More Related Videos

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD08:29

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Published on: October 10, 2012

A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure09:06

A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure

Published on: October 24, 2018

Related Concept Videos

Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
Physiological Foundation of Stress01:24

Physiological Foundation of Stress

Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
The Sympathetic Nervous System01:25

The Sympathetic Nervous System

Overview