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Related Experiment Video

Updated: Mar 16, 2026

The Forced Swim Test as a Model of Depressive-like Behavior
05:42

The Forced Swim Test as a Model of Depressive-like Behavior

Published on: March 2, 2015

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A2 noradrenergic neurons regulate forced swim test immobility.

Hyungwoo Nam1, Ilan A Kerman2

  • 1Department of Anatomy and Neurobiology, University of Maryland School of Medicine, United States.

Physiology & Behavior
|August 25, 2016
PubMed
Summary

Wistar-Kyoto rats, a depression model, show altered brainstem noradrenergic cell activation. Specifically, reduced A2 noradrenergic cell activity contributes to their unique immobility behavior in the forced swim test.

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Animal Models

Background:

  • The Wistar-Kyoto (WKY) rat is a key animal model for studying depression, exhibiting distinct noradrenergic signaling dysregulation.
  • WKY rats display unique forced swim test (FST) behaviors, including initial high immobility and increased immobility upon re-exposure, differing from Wistar rats.

Purpose of the Study:

  • To investigate if altered activation of brainstem noradrenergic cell groups contributes to the unique behavioral profile of WKY rats in the FST.
  • To compare the activation patterns of noradrenergic cell groups in WKY and Wistar rats under different FST conditions.

Main Methods:

  • WKY and Wistar rats were subjected to either a single 5-minute FST or a standard two-day FST.
  • Brain tissue was analyzed using FOS/tyrosine hydroxylase double-immunocytochemistry to assess noradrenergic cell group activation.
Keywords:
BehaviorDepressionForced swim testFosRat

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  • Selective lesions of A2 noradrenergic neurons were induced in Wistar rats using anti-dopamine-β-hydroxylase-conjugated saporin.
  • Main Results:

    • WKY rats showed relative hyperactivation in the locus coeruleus compared to Wistar rats following both one- and two-day FST protocols.
    • WKY rats exhibited diminished FOS expression in the A2 noradrenergic cell group across both FST days, indicating reduced activation.
    • Lesioning A2 noradrenergic neurons in Wistar rats led to increased immobility in the FST on both days.

    Conclusions:

    • The A2 noradrenergic cell group plays a regulatory role in FST behavior.
    • Hypoactivation of the A2 noradrenergic cell group may underlie the distinct behavioral phenotype observed in WKY rats, contributing to depression-like behaviors.