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A New Method for Inducing a Depression-Like Behavior in Rats
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Repeated gadolinium-based contrast agent exposure increases depression-like behavior in rats.

Jeho Seo1, Hyewon Oh2, Ga Bin Park2

  • 1Department of Emergency Medicine, Incheon Korean Veteran Health Service, Incheon, Republic of Korea.

Japanese Journal of Radiology
|November 10, 2025
PubMed
Summary

Repeated administration of gadolinium-based contrast agents (GBCAs) in rats did not affect locomotor activity or anxiety. However, GBCAs were associated with increased depression-like behavior, indicating potential neurological effects.

Keywords:
Animal studyAnxietyGadolinium-based contrast agentsLearned helplessness

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Toxicology

Background:

  • Gadolinium-based contrast agents (GBCAs) are widely used in medical imaging.
  • Concerns exist regarding potential long-term effects of gadolinium retention in the brain.
  • Understanding the neurobehavioral impact of repeated GBCA exposure is crucial for patient safety.

Purpose of the Study:

  • To investigate the behavioral consequences of repeated administration of GBCAs in a rat model.
  • To assess changes in locomotor activity, anxiety-like behavior, and depression-like behavior following GBCA exposure.
  • To correlate brain gadolinium deposition with observed behavioral alterations.

Main Methods:

  • Rats received repeated intravenous administrations of gadodiamide (linear GBCA), gadobutrol (macrocyclic GBCA), or saline over two weeks.
  • Behavioral assessments, including the open field test and learned helplessness test, were conducted post-administration.
  • Brain tissue was analyzed for gadolinium concentration using ICP-MS.

Main Results:

  • Gadolinium retention was significantly higher in rats treated with both gadodiamide and gadobutrol compared to saline controls.
  • No significant differences in locomotor activity or anxiety-like behavior were observed between GBCA-treated groups and the control group.
  • Rats administered GBCAs exhibited a significant increase in depression-like behavior, as evidenced by higher escape failures and longer escape times in the learned helplessness test.

Conclusions:

  • Repeated GBCA administration in rats leads to increased depression-like behavior.
  • No significant impact on locomotor activity or anxiety was detected.
  • These findings suggest potential neurotoxic effects of GBCAs, particularly concerning mood regulation, warranting further investigation.