Repeated gadolinium-based contrast agent exposure increases depression-like behavior in rats.

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.