Original Article

Neuropsychopharmacology (2006) 31, 1919–1927. doi:10.1038/sj.npp.1300998; published online 4 January 2006

Preclinical Research

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

Kally C O'Reilly1, Jason Shumake2, F Gonzalez-Lima2, Michelle A Lane1,3,5 and Sarah J Bailey4,5

  1. 1Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA
  2. 2Department of Psychology, The University of Texas at Austin, Austin, TX, USA
  3. 3Division of Nutritional Sciences, Department of Human Ecology, The University of Texas at Austin, Austin, TX, USA
  4. 4Department of Pharmacy and Pharmacology, University of Bath, Bath, UK

Correspondence: Dr MA Lane, Division of Nutritional Sciences, Department of Human Ecology, Gearing Hall Room 115, Mail Stop A2700, The University of Texas at Austin, Austin, TX 78712, USA. Tel: +1 512 232 9410; Fax: +1 512 471 5844; E-mail: mlane@mail.utexas.edu

5These authors contributed equally to this work.

Received 8 August 2005; Revised 24 October 2005; Accepted 27 October 2005; Published online 4 January 2006.



Retinoid signaling plays a well-established role in neuronal differentiation, neurite outgrowth, and the patterning of the anteroposterior axis of the developing neural tube. However, there is increasing evidence that nutritional vitamin A status and retinoid signaling play an important role in the function of the adult brain. 13-Cis-retinoic acid (13-cis-RA) (isotretinoin or Accutane), a synthetic retinoid that is an effective oral treatment for severe nodular acne, has been linked with depression and suicide in patients. The purpose of this study was to test the hypothesis that chronic administration of 13-cis-RA would lead to depression-related behaviors in mice. Young, adult male mice received 13-cis-RA (1 mg/kg) by daily intraperitoneal injection for 6 weeks. This treatment paradigm produced plasma levels of 13-cis-RA that are comparable to those reported in human patients taking Accutane. In both the forced swim test and the tail suspension test, we found that 13-cis-RA-treated mice spent significantly more time immobile compared to vehicle-treated controls. In the open field test, there was no change in anxiety-related behavior in 13-cis-RA-treated mice. Furthermore, chronic administration of 13-cis-RA did not impair locomotion in either the open field or the rotarod test. Taken together, these results suggest that administration of 13-cis-RA increases depression-related behaviors in mice.


isotretinoin, Accutane, forced swim test, tail suspension test, depression, mice

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