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

To evaluate behavioral changes in rats after repeated gadolinium-based contrast agent (GBCA) administrations, focusing on locomotor activity, anxiety, and depression-like behavior.

Gadodiamide (linear GBCA), gadobutrol (macrocyclic GBCA), or saline were administered via the tail vein every 2 days for 2 weeks (n = 12/group, 6 injections). Behavior tests were conducted 3 days after the final administration. Locomotor activity and anxiety-like behavior were assessed using the open field test and depression-like behavior with the learned helplessness test. Gadolinium concentration in the brain was measured by inductively coupled plasma mass spectrometry (ICP-MS). Data were presented as means ± standard deviation (S.D.).

Gd retention decreased from gadodiamide (1.061 ± 0.162 μg/g), gadobutrol (0.291 ± 0.098 μg/g) to saline (0.027 ± 0.090 μg/g; P < 0.001) administration. In the open field test, total distance moved (control = 2451.2 ± 316.3 cm, gadodiamide = 2574.3 ± 318.6 cm, gadobutrol = 2835.5 ± 563.5 cm, P = 0.080) and center time (control = 2.3 ± 1.8%, gadodiamide = 1.7 ± 1.7%, gadobutrol = 1.6 ± 1.3%, P = 0.540) didn't differ between groups. In the learned helplessness test, escape failures and times were higher for gadodiamide (16.0 ± 8.2 times, P = 0.020; 14.6 ± 6.1 s, P = 0.030) and gadobutrol (17.5 ± 8.5 times, P = 0.007; 16.0 ± 7.3 s, P = 0.010) than saline (8.3 ± 6.7 times, 9.4 ± 5.0 s). Learned helplessness was higher with gadodiamide (6/12) and gadobutrol (7/12) administration than saline (1/12; P < 0.001).

In rats repeatedly administered GBCA, no locomotor activity or anxiety was observed, but depression-like behavior increased.