Abstract.
Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT –/– mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/– mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/– and +/+ mice, but not in 5-HTT –/– mice. 5-HTT –/– mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/– and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/– and +/+, but not 5-HTT –/– mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice.
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Holmes, A., Murphy, D.L. & Crawley, J.N. Reduced aggression in mice lacking the serotonin transporter. Psychopharmacology 161, 160–167 (2002). https://doi.org/10.1007/s00213-002-1024-3
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DOI: https://doi.org/10.1007/s00213-002-1024-3