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Chronic treatment of rats with 13-cis retinoic acid changes aggressive behaviours in the resident-intruder paradigm 13-Cis retinoic acid (13-cis-RA, Roaccutane) is a vitamin A derivative that is prescribed for severe cystic acne in humans. Controversially, its use is associated with the onset of psychiatric symptoms such as depression and suicide (Hull et al., 2003). Previous animal studies with adolescent mice have indicated that chronic treatment with 13-cis RA increases depressive indices in the forced swim test and tail suspension test (O’Reilly et al., 2006). However, chronic studies with adult rats have shown no change in depression-related behaviour (Ferguson et al., 2005). To further investigate the behavioural deficits caused by 13-cis RA we employed the resident-intruder paradigm to measure the agonistic behaviour of resident rats towards intruder rats (Mitchell et al., 1992). The model is sensitive to the chronic effects of antidepressant treatment, such that chronic treatment with selective serotonin reuptake inhibitors selectively increases aggressive behaviour, which reflects the increased assertiveness seen during the recovery from depressive illness in humans (Mitchell, 2005). Day-night reversed adult male Wistar rats (n=8 per group, 230-300g pre-treatment weight) were treated daily with 1mg/kg intraperitoneal injections of 13-cis RA for 14 days. A vehicle-control group received 0.9% w/v saline:DMSO (1:1 v/v). Encounters between resident and intruder rats were recorded onto videotape (10 min), with subsequent ethological analysis of behaviour (Mitchell et al., 1992). All behaviours were expressed as the mean (± SEM) percentage of total behaviour exhibited. Data were analyzed by one-way ANOVA with repeated measures. Significant interactions between treatment and time were observed for aggression, flight-submit and flight-escape behaviours [all Fs (3,42) ³ 3.279; p< 0.05 in all cases]. Post-hoc analysis (one-way ANOVA) revealed that resident rats treated with 13-cis RA displayed reduced aggressive behaviour and increased flight behaviour at 7 and 14 days of treatment (see table, p< 0.01 in all cases compared to vehicle-controls). No differences were recorded between 13-cis RA and vehicle groups both pre-treatment and post-treatment.
These results show for the first time that 13-cis RA administration in adult rats produces a behavioural profile in the resident-intruder paradigm that is directly opposite to that of chronic antidepressant administration and further implicates the drug in causing pro-depressive effects. Hull et al., 2003 Am J Clin Dermatol. 4 :493-505. |
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