Citation

Ferguson SA, Cisneros FJ, Gough B, Hanig JP, Berry KJ. Toxicol. Sci. 2005; 87(2): 451-459.

Copyright

(Copyright © 2005, Oxford University Press)

DOI

10.1093/toxsci/kfi262

PMID

16033993

Abstract

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.

Language: en

Keywords

Aging; Animals; Behavior, Animal; Body Weight; Depression; Dose-Response Relationship, Drug; Drinking; Eating; Female; Isotretinoin; Keratolytic Agents; Male; Motor Activity; Rats; Saccharin; Sex Characteristics; Sweetening Agents; Swimming; Tretinoin