Long-term citalopram maintenance in mice: selective reduction of alcohol-heightened aggression

Background Selective serotonin reuptake inhibitors (SSRIs) alleviate many affective disturbances in human clinical populations and are used in animal models to study the influence of serotonin (5-HT) on aggressive behavior and impulsivity. Objective We hypothesized that long-term SSRI treatment may reduce aggressive behavior escalated by alcohol consumption in mice. Therefore, aggression was tested in male CFW mice to determine whether repeated citalopram (CIT) administration reduces alcohol-heightened aggression. Materials and methods Resident male mice self-administered alcohol by performing an operant response on a panel placed in their home cage that delivered a 6% alcohol solution. Mice repeatedly confronted an intruder 15 min after self-administration of either 1 g/kg alcohol (EtOH) or water (H₂O). Aggressive behaviors were higher in most mice when tests occurred after EtOH intake relative to H₂O. Once baseline aggression was established, animals were injected (i.p.) twice daily with 10 mg/kg CIT or saline (SAL) for 32 days. Every 4 days throughout the CIT treatment period, aggressive encounters occurred 6 h after CIT injections, with testing conditions alternating between EtOH and H₂O intake. Results Aggression was only modestly affected by CIT in the first 2 weeks of treatment. However, by day 17 of CIT treatment, alcohol-heightened aggressive behavior was abolished, while baseline aggression remained stable. These data lend support for the role of the 5-HT transporter in the control of alcohol-related aggressive behavior, and the time course of effects suggests that a change in density of 5HT_1A autoreceptors is necessary before antidepressant drugs produce beneficial outcomes.