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

• Published in: Toxicological sciences Vol. 87; no. 2; pp. 451 - 459
• Main Authors: Ferguson, Sherry A., Cisneros, F. Javier, Gough, B., Hanig, Joseph P., Berry, Kimberly J.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2005
• Subjects: 13-cis-retinoic acid; Aging - psychology; all-trans-retinoic acid; anhedonia; Animals; Behavior, Animal - drug effects; Body Weight - drug effects; depression; Depression - psychology; Dose-Response Relationship, Drug; Drinking - drug effects; Eating - drug effects; Female; Forced Swim Test; isotretinoin; Isotretinoin - toxicity; Keratolytic Agents - toxicity; locomotor activity; Male; Motor Activity - drug effects; Rats; Saccharin; Sex Characteristics; Sweetening Agents; Swimming - psychology; Tretinoin - toxicity
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfi262

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.