Behavioral and Neuronal Changes Due to 13-Cis-Retinoic Acid Treatment

The use of 13-cis-RA to treat severe acne has been associated with onset of depression in the humans, although whether or not 13-cis-RA can cause depression has remained controversial. Because the psychosocial impact of acne may play a factor in adolescent depression, an animal model was used to test the hypothesis that chronic administration of 13-cis-RA would lead to depression-related behaviors. Young, adult male mice received 13-cis-RA (1 mg/kg) by daily i.p. 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.