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

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Abstract

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 5HT1A autoreceptors is necessary before antidepressant drugs produce beneficial outcomes.

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Acknowledgments

This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (USPHS Award AA013983 and Fellowship Award F32AA015013).

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Medford, MA, 02155, USA

    Elizabeth E. Caldwell & Klaus A. Miczek

  2. Departments of Psychiatry, Pharmacology and Experimental Therapeutics, and Neuroscience, Tufts University, Boston, MA, 02118, USA

    Klaus A. Miczek

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  1. Elizabeth E. Caldwell
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Correspondence to Klaus A. Miczek.

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Caldwell, E.E., Miczek, K.A. Long-term citalopram maintenance in mice: selective reduction of alcohol-heightened aggression. Psychopharmacology 196, 407–416 (2008). https://doi.org/10.1007/s00213-007-0972-z

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