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ToxSci Advance Access originally published online on July 20, 2005
Toxicological Sciences 2005 87(2):451-459; doi:10.1093/toxsci/kfi262
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Published by Oxford University Press 2005.

Chronic Oral Treatment with 13-cis-Retinoic Acid (Isotretinoin) or all-trans-Retinoic Acid Does Not Alter Depression-Like Behaviors in Rats

Sherry A. Ferguson*,1, F. Javier Cisneros*, B. Gough*, Joseph P. Hanig{dagger} and Kimberly J. Berry*

* Division of Neurotoxicology, National Center for Toxicological Research/U.S. Food and Drug Administration, Jefferson, Arkasas 72079; {dagger} Center for Drug Evaluation Research/U.S. Food and Drug Administration, Silver Spring, Maryland

Received June 14, 2005; accepted July 8, 2005

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130–131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102–104 and PND 151–153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg–treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

Key Words: isotretinoin; 13-cis-retinoic acid; all-trans-retinoic acid; depression; anhedonia; locomotor activity; Forced Swim Test.


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