Chronic treatment with 13-cis-retinoic acid changes aggressive behaviours in the resident-intruder paradigm in rats

Retinoids, vitamin A related compounds, have an established role in the development of the nervous system and are increasingly recognized to play a role in adult brain function. The synthetic retinoid, 13-cis-retinoic acid (13-cis-RA, Roaccutane) is widely used to treat severe acne but has been linked to an increased risk of neuropsychiatric side effects, including depression. Here we report that chronic administration with 13-cis-RA (1 mg/kg i.p. daily, 7-14 days) in adult rats reduced aggression- and increased flight-related behaviours in the resident-intruder paradigm. However, in the forced swim, sucrose consumption and open field tests treatment for up to 6 weeks with 13-cis-RA did not modify behaviour in adult or juvenile animals. The behavioural change observed in the resident-intruder paradigm is directly opposite to that observed with chronic antidepressant administration. These findings indicate that when a suitably sensitive behavioural test is employed then chronic administration of 13-cis-RA in adult rats induces behavioural changes consistent with a pro-depressant action.