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

Abstract

PURPOSE: To evaluate behavioral changes in rats after repeated gadolinium-based contrast agent (GBCA) administrations, focusing on locomotor activity, anxiety, and depression-like behavior. MATERIAL AND METHODS: Gadodiamide (linear GBCA), gadobutrol (macrocyclic GBCA), or saline were administered via the tail vein every 2&#xa0;days for 2&#xa0;weeks (n&#x2009;=&#x2009;12/group, 6 injections). Behavior tests were conducted 3&#xa0;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&#x2009;&#xb1;&#x2009;standard deviation (S.D.). RESULTS: Gd retention decreased from gadodiamide (1.061&#x2009;&#xb1;&#x2009;0.162&#xa0;&#x3bc;g/g), gadobutrol (0.291&#x2009;&#xb1;&#x2009;0.098&#xa0;&#x3bc;g/g) to saline (0.027&#x2009;&#xb1;&#x2009;0.090&#xa0;&#x3bc;g/g; P&#x2009;<&#x2009;0.001) administration. In the open field test, total distance moved (control&#x2009;=&#x2009;2451.2&#x2009;&#xb1;&#x2009;316.3&#xa0;cm, gadodiamide&#x2009;=&#x2009;2574.3&#x2009;&#xb1;&#x2009;318.6&#xa0;cm, gadobutrol&#x2009;=&#x2009;2835.5&#x2009;&#xb1;&#x2009;563.5&#xa0;cm, P&#x2009;=&#x2009;0.080) and center time (control&#x2009;=&#x2009;2.3&#x2009;&#xb1;&#x2009;1.8%, gadodiamide&#x2009;=&#x2009;1.7&#x2009;&#xb1;&#x2009;1.7%, gadobutrol&#x2009;=&#x2009;1.6&#x2009;&#xb1;&#x2009;1.3%, P&#x2009;=&#x2009;0.540) didn't differ between groups. In the learned helplessness test, escape failures and times were higher for gadodiamide (16.0&#x2009;&#xb1;&#x2009;8.2 times, P&#x2009;=&#x2009;0.020; 14.6&#x2009;&#xb1;&#x2009;6.1&#xa0;s, P&#x2009;=&#x2009;0.030) and gadobutrol (17.5&#x2009;&#xb1;&#x2009;8.5 times, P&#x2009;=&#x2009;0.007; 16.0&#x2009;&#xb1;&#x2009;7.3&#xa0;s, P&#x2009;=&#x2009;0.010) than saline (8.3&#x2009;&#xb1;&#x2009;6.7 times, 9.4&#x2009;&#xb1;&#x2009;5.0&#xa0;s). Learned helplessness was higher with gadodiamide (6/12) and gadobutrol (7/12) administration than saline (1/12; P&#x2009;<&#x2009;0.001). CONCLUSION: In rats repeatedly administered GBCA, no locomotor activity or anxiety was observed, but depression-like behavior increased.